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Velasco, Sánchez Ana. "Oncogenes y genes supresores de tumores en carcinoma de endometrio." Doctoral thesis, Universitat de Lleida, 2012. http://hdl.handle.net/10803/110545.
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El objetivo principal de este trabajo ha sido la identificación de alteraciones moleculares que participen de manera significativa en el desarrollo y la progresión del cáncer de endometrio, con el propósito de añadir mas claves para el descubrimiento de nuevas dianas de diagnosis y terapias individuales contra esta patología. El trabajo ha sido centrado en el estudio de modificaciones en el ADN de las células que forman el tejido tumoral en una serie de pacientes con carcinoma endometrial, en concreto, en el análisis mutacional de los genes PIK3CA y FGFR2 y el análisis de hipermetilación del promotor de los genes RASSF2A y SPRY2, elementos que forman parte de importantes vías de transducción de señales implicadas principalmente en procesos de crecimiento y diferenciación celular. Por un lado, hemos advertido cierto grado de variabilidad en el patrón de expresión de los genes estudiados en los tejidos tumoral y no tumoral y esas diferencias de expresión son, en parte, debidas a la existencia de hipermetilación en las regiones promotoras de los genes implicados. Así mismo, la presencia de mutaciones en regiones génicas que codifican partes de la proteína claves para su función en la célula es también un factor que modifica el patrón de expresión entre tejidos. En concreto, tras el análisis de la expresión inmunohistoquímica de RASSF1A y la presencia o ausencia de metilación en la zona promotora del gen RASSF1A se detectaron tumores con niveles de expresión reducidos y presencia de hipermetilación en el promotor, ambos fenómenos asociados de manera estadísticamente significativa. Lo mismo ocurre, aunque en un grado distinto, con la expresión de SPRY2 en algunos tumores en asociación con la presencia de hipermetilación en el promotor del gen. A través de este análisis hemos descubierto que la expresión de SPRY2 presenta variabilidad en las glándulas endometriales de los tejidos no tumorales a lo largo del ciclo menstrual. Por otro lado hemos visto como el gen PIK3CA se encuentra frecuentemente mutado en las células que forman los tumores de carcinoma de endometrio y que, además, es un suceso que coincide con la presencia de mutaciones en el gen PTEN. Sin embargo, la frecuencia de mutaciones en el gen FGFR2 se ha mostrado baja aunque su expresión a nivel inmunohistoquímico refleja diferencias entre carcinoma de tipo endometrioide y no endometrioide. Por ultimo, añadir una revisión de uno de los fenómenos que ocurren de manera mas frecuente durante la formación y el progreso de los tumores en carcinoma de endometrio: el concepto de “pérdida de heterocigosidad”. En este trabajo hemos considerado primordial incluir un obra en la que se realiza una incursión a los mecanismos moleculares a través de los cuales se produce la pérdida de heterocigosidad, asi como los métodos que se utilizan para su detección y el significado de algunos patrones de pérdida de heterocigosidad en determinadas regiones cromosómicas en carcinoma de endometrio.L'objectiu principal d'aquest treball ha estat la identificació d'alteracions moleculars que participin de manera significativa al desenvolupament i la progressió del càncer d'endometri, amb el propòsit d'afegir més claus pel descobriment de noves dianes de diagnosi i teràpies individuals contra aquesta patologia. El treball ha estat centrat en l’estudi de modificacions en l’ADN de les cèl-lules que formen el teixit tumoral en una sèrie de pacients amb carcinoma endometrial, en concret, en l’anàlisi mutacional del gens PIK3CA i FGFR2 i l’anàlisi de hipermetilació del promotor dels gens RASSF1A i SPRY2, elements que formen part d’importants vies de transducció de senyals implicades principalment en processos de creixement i diferenciació cel-lular. En primer lloc hem advertit cert grau de variabilitat en el patró d'expressió dels gens estudiats entre els teixits tumoral i no tumoral i aquestes diferències d'expressió són, en part, degudes a l'existència de hipermetilació en les regions promotores dels gens implicats. Així mateix, la presencia de mutacions en regions gèniques que codifiquen parts de la proteïna claus per la seva funció a la cèl-lula, és també un factor que modifica el patró d'expressió entre entre els teixits tumoral i no tumoral. En concret, després de l’anàlisi immunohistoquímic de l’expressió de RASSF1A i la presència o absència de metilació a la zona promotora del gen RASSF1A, es van detectar tumors amb nivells d’expressió reduïts i presència de hipermetilació en el promotor, ambdós fenòmens associats de manera estadísticament significativa. El mateix passa, encara que amb diferent grau, amb l’expressió de SPRY2 en alguns tumors en associació amb la presència de ipermetilació en el promotor del gen. A través d’aquest anàlisi hem descobert que l’expressió de SPRY2 presenta variabilitat en les glàndules endometrials dels teixits no tumorals al llarg del cicle menstrual. D'altra banda hem vist com el gen PIK3CA es troba freqüentment mutat en les cèl-lules que formen els tumors de carcinoma d'endometri i coincideix amb la presència de mutacions en el gen PTEN. No obstant això, la freqüència de mutacions en el gen FGFR2 s'ha mostrat baixa encara que la seva expressió a nivell inmunohistoquímic reflecteix diferencies entre carcinoma de tipus endometrioide y no endometrioide. Finalment, afegir una revisió d'un dels fenòmens més freqüent en la formació i el progrés dels tumors en carcinoma d'endometri: el concepte de "pèrdua de heterozigositat". En aquest treball hem considerat primordial incloure una obra en que es realitza una incursió als mecanismes moleculars a través dels quals es produeix la pèrdua de heterozigositat, aixi com els mètodes que s'utilitzen en la seva detecció i el significant d'alguns patrons de pèrdua de heterozigositat en determinades regions cromosòmiques en carcinoma d'endometri.
The main point of this study was the identification of molecular alterations that participate in the development and progression of endometrial cancer, in order to add more keys to the discovery of new targets for diagnosis and therapies against this disease. The work has been focused on the study of molecular alterations of DNA from tumour tissues in a series of endometrial carcinoma patients, above all, mutational analysis of PIK3CA and FGFR2 genes and analysis of promoter hyper methylation of SPRY2 and RASSF2A genes, together forming part of signal transduction pathways that are involved in processes of growth and cell differentiation. To begin with, we noticed some variability in the gene expression pattern examined between tumour and normal tissue, and these differences are partly due to hyper methylation in promoter regions at the involved genes. Likewise, mutations in gene regions encoding key protein domains in the cell are also a factor that modifies the gene expression pattern between tumour and normal tissue. In particular, after analysing the immunohistochemical expression of RASSF1A and the presence or absence of methylation in the RASSF1A gene promoter we detected tumours with low expression levels and promoter hyper methylation. The same applies, albeit in a different degree, with SPRY2 expression in some tumours in association with the presence of gene promoter hyper methylation. Through this analysis we found some SPRY2 expression variability in endometrial glands from non-tumour tissues throughout the menstrual cycle. On the other hand we have seen that the PIK3CA gene is frequently mutated in tumour cells from endometrial carcinoma, and this is also a PTEN gene mutation coincident event. However, FGFR2 gene mutation ratio has shown to be low although immunohistochemical expression reflects differences between endometrioid endometrial carcinoma and no-endometrioid type. Finally, we wanted to add a review of one of the phenomena, which occurs more frequently during the formation and progress of tumours in endometrial carcinoma: LOH "loss of heterozygosity". We have considered essential include a review work about the molecular mechanisms through which loss of heterozygosity is produced, the methods used in their detection and significance of some patterns of loss of heterozygosity in specific chromosomal regions in endometrial carcinoma.
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Tonon, Ângela Favorito Santarém [UNESP]. "Claudina-3 e Claudina- 4, potenciais marcadores de agressividade no carcinoma endometrial Tipo I." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/108608.
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000758246.pdf: 1669883 bytes, checksum: ace7f36bd830a8ef0026e86e6c1f9acb (MD5)O Carcinoma de Endométrio é a neoplasia epitelial maligna que acomete mulheres no pré, pós e peri -menopausa. Segundo diferenças endócrinas, metabólicas, fatores de risco e morfologia é classificado em dois grandes grupos: Tipo I (endometrióide) e Tipo II (não endometrióide). O Tipo I perfaz 90 % dos carcinomas de endométrio e sua patogenia esta ligada a exposição excessiva ao estrógeno. O Tipo II é incomum, com fatores predisponentes menos conhecidos. O sintoma mais relevante do carcinoma de endométrio é o sangramento pós-menopausa. Seu diagnóstico é feito pela comprovação histológica, associada aos exames de imagem e laboratoriais. Seu tratamento é fundamentalmente cirúrgico. O fator prognóstico mais importante é a presença ou ausência de metástase nos linfonodos regionais. Atualmente, buscam-se marcadores biológicos e teciduais que indiquem pior prognóstico. Este trabalho verificou a imunoexpressão da claudina-3 (CLDN3) e claudina-4 (CLDN4) nos carcinomas de endométrio Tipo I e Tipo II, relacionando-as com endométrio proliferativo e atrófico, aspectos clínicos, anatomopatológicos, perfil hormonal, índice de proliferação celular e expressão da p53, na tentativa de estabelecer a importância destas proteínas na progressão e agressividade tumoral e o seu valor prognóstico. Foram estudados 79 casos de carcinoma de endométrio e comparados com 74 endométrios normais. Avaliou-se a imunoexpressão das CLDNs 3 e 4, receptor estrogênico, receptor de progesterona, índice de proliferação celular (Ki67) e p53, pela técnica de imunoistoquímica. Observou-se que o padrão de coloração da membrana para CLDN3 se mostrou difuso nos carcinomas, quando comparado com os endométrios normais que exibiu padrão focal. O número de células marcadas com CLDN3 estava diminuído nos carcinomas Tipo I, porém com intensidade aumentada. Nesta análise foi possível verificar que ...
Carcinoma of the Endometrium is a malignant epithelial tumor which affects pre, peri and post-menopausal women. It is classified into two major groups, according to endocrine, metabolic risk factors and morphological differences: Type I (endometrioid) and Type II (non-endometrioid). Type I accounts for 90% of all endometrial carcinomas and its pathogenesis is linked to excessive estrogen exposure. The Type II is less common, with poorly defined predisposing factors. The most important symptom of endometrial carcinoma is postmenopausal bleeding. Diagnosis is achieved through histological evidence, in association with imaging and laboratorial exams. Treatment is primarily surgical. The most important prognostic factor is the presence or absence of metastases in regional lymph nodes. Bio and tissue markers that indicate worse prognosis are the focus of current research. This study examined the immunoexpression of claudin-3 (CLDN3) and claudin-4 (CLDN4) in endometrial carcinomas Type I and Type II, and their relation to proliferative and atrophic endometrium, clinical and pathological features, hormonal status, proliferation index and p53 expression, in an attempt to establish the importance of these proteins in tumor progression and aggressiveness and their prognostic value. Seventy-nine cases of endometrial carcinoma were studied and compared with 74 normal endometria. The immunoexpression of CLDNs 3 and 4, estrogen receptor, progesterone receptor, cell proliferation index (Ki67) and p53 were all evaluated by immunohistochemistry. Observation verified that the pattern of membrane staining for CLDN3 was diffuse in carcinomas compared with normal endometrium which presented a focal pattern. The number of cells stained with CLDN3 was lower in Type I carcinomas, while staining intensity was greater. Analysis verified that 25% of cases with high expression of CLDN4 and Ki-67 developed metastasis, while 33% of cases with greater CLDN4 staining ...
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Lombardelli, Karen Vicencia Pingarilho. "Ressonancia magnetica resumida na avaliação da extensão do carcinoma de endometrio." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310562.
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Orientador: Luiz Carlos ZeferinoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Introdução: A ressonância magnética (RM) é um exame que pode auxiliar no estadiamento pré-cirúrgico da paciente com carcinoma de endométrio, o que permite planejar mais adequadamente a cirurgia, principalmente quando há evidências de doença avançada e em mulheres com comorbidades clínicas relevantes. Todavia, é um exame demorado, exige cooperação e imobilidade, emite ruído e o espaço físico é restrito, ocasionando desconforto e claustrofobia. Motivos referidos, inclusive como justificativa de interrupção do exame. A mobilidade durante o exame, incluindo movimentos respiratórios acentuados, assim como o alto índice de obesidade em mulheres com carcinoma de endométrio podem gerar artefatos que comprometem a qualidade da imagem, prejudicado o diagnóstico final. Simplificar o exame com redução do tempo de duração sem prejudicar a qualidade do diagnóstico seria muito útil. Objetivos: O objetivo deste estudo foi avaliar se a subtração das seqüências T1 FS sagital e T2 TSE coronal, sem contraste e com aquisições de alta resolução, comprometeria o desempenho diagnóstico na avaliação da extensão do carcinoma de endométrio. Material e Métodos: Este estudo foi observacional e descritivo, de corte transversal. Foram incluídas 62 mulheres com diagnóstico histológico de carcinoma de endométrio. As pacientes fizeram RM da pelve que foi analisada por dois médicos especialistas, sendo que um avaliou o exame completo e o outro o exame resumido, sem troca de informações entre eles. Os achados da RM completa e resumida foram comparados com os laudos anatomopatológicos. Para testar a associação entre as variáveis qualitativas foi utilizado o teste qui-quadrado. A concordância diagnóstica entre os exames completo e resumido da RM foi analisada pelo Coeficiente de Kappa. Resultados: As medianas, médias, desvios-padrão e valores máximos das medidas do maior diâmetro do tumor avaliadas pelas RMC, RMR e patologia foram muito próximas. As medianas, médias, desvios-padrão, valores mínimos e valores máximos do volume do tumor avaliado pelas RMC e RMR foram muito próximos. A mediana do volume do tumor avaliado pela patologia foi muito próxima das medianas obtidas pela ressonância magnética, enquanto que a média, desvio-padrão e valor máximo apresentaram valores maiores. Conclusões: A RMR apresenta desempenho semelhante ao da RMC na avaliação da extensão do carcinoma do endométrio. A concordâncJa observada para avaliação da invasão, miometrial, do colo do útero e dos linfonodos pélvicos foi classificada como muito boa ou excelente. A concordância na avaliação da invasão do colo do útero entre a patologia e as RMC e RMR foi classificada como muito boa (Tabela 2). A concordância observada para avaliação das invasões miometrial e do colo do útero entre os exames de RM foi classificada como muito boa ou excelente. Portanto, é possível utilizar o exame de RM sem as seqüências T1 SE sagital sem contraste e T2 TSE caronal, pois não haverá prejuízo na qualidade do diagnóstico
Abstract: Background: Magnetic resonance imaging (MRI) is an exam that may be helpful in establishing presurgical staging of patients with endometrial carcinoma, allowing a more appropriate surgical procedure to be planned, principally in the case of advanced disease or in women with relevant clinical comorbidities. However, it is a protracted exam that requires cooperation and immobility. In addition, it is noisy and physical space is restricted, often causing discomfort, anxiety and claustrophobia that may lead to interruption of the exam. Movements including accentuated breathing may generate artifacts that compromise the quality of images. Simplifying the exam by reducing the time required to carry it out without affecting the quality of diagnosis would be extremely useful. Objectives: To evaluate whether modification to the routine MRI (complete MRI) by eliminating the non contrast high resolution sagittal T1-weighted FS and caronal T2-weighted TSE sequences (resumed MRI), negatively affects performance of this exam in the diagnosis of the extent of endometrial carcinoma. Methods: A cross sectional, observational, descriptive study was carried out in 62 women with endometrial carcinoma. All underwent pelvic MRI, which was analyzed by two radiologists. Complete and rapid MRI findings were compared with anatomopathology reports. The chi-square test was used to test the association between qualitative variables. Diagnostic agreement between complete and resumed MRI was analyzed using the kappa coefficient. Results: There were no statistically significant differences in the medians, means, standard deviations or maximum values of the measurements of the greatest diameter and of tumor volume as evaluated by complete MRI, resumed MRI and pathology. With respect to myometrial invasion, agreement between complete and resumed MRI was classified as very good, with a kappa coefficient of 0.73 (0.54 - 0.93). Agreement in the evaluation of myometrial invasion between pathology and complete or resumed MRI was classified as good. With respect to cervical invasion, agreement between complete and rapid MRI was classified as excellent, with a kappa coefficient of 0.96 (0.87 - 1.00). Agreement in the evaluation of cervical invasion between pathology and complete and resumed MRI was classified as very good. With respect to pelvic Iymph nodes, agreement between complete and resumed MRI was classified as excellent, with kappa coefficients of 0.93 (0.84 - 1.00) and 0.96 (0.90 - 1.00), respectively. Conclusions: MRI without the non-contrast sagittal T1-weighted SE and coronal T2-weighted TSE sequences maintains the same performance as complete MRI in evaluating the extent of endometrial carcinoma. The shorter time required to carry out the exam would, therefore, be beneficial to the patients, reducing their discomfort and, principally, decreasing reactions of anxiety and claustrophobia. Moreover, costs to healthcare services, and indirectly to the patients, would also be reduced, since the productivity of the equipment and the team would be higher
Mestrado
Ciencias Biomedicas
Mestre em Tocoginecologia
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Testoni, Blasco di Sciacca Alessandra Lucia Maria. "Metalloproteasi 9, TIMP-1 e Osteopontina quali possibili biomarcatori del carcinoma dell endometrio." Doctoral thesis, Università di Catania, 2012. http://hdl.handle.net/10761/1217.
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Lo scopo del nostro lavoro è stato quello di valutare l esistenza di una diversa espressione tissutale e periferica di metalloproteasi MMP9, TIMP1 (la sua proteina inibitoria) e Osteopontina, quali possibili biomarcatori di progressione tumorale, in donne con patologie benigne dell endometrio, con carcinoma dello stesso, e di un gruppo di donne come controllo.
Abbiamo reclutato per il nostro studio 31 pazienti che si erano sottoposte ad un esame isteroscopico o per sanguinamenti anomali, o per un ispessimento endometriale evidenziato durante un ecografia ginecologica. Lo stesso giorno in cui alle pazienti veniva eseguita l isteroscopia della cavità uterina, sono stati prelevati circa 10 ml di sangue venoso periferico, suddivisi in due provette: 2-3 ml per la raccolta del siero e 6-7 ml per la raccolta del plasma, con aggiunta di Na++ eparina. Le provette sono state quindi inviate, entro 30 minuti, per la loro centrifugazione ed i campioni di plasma e siero aliquotati, sono stati conservati a -80°C, fino al momento del saggio. Successivamente sono stati eseguiti i dosaggi in ELISA su siero o plasma delle tre proteine da noi considerate, con Kits disponibili commercialmente secondo la metodica indicata dal produttore (R e D System). In corso di isteroscopia, sono state praticate delle biopsie della cavità uterina o dei polipi endometriali. Un piccolo frammento tissutale veniva raccolto in Rna Later, e conservato ad una temperatura di -80°C fino alle indagini di biologia molecolare (estrazione dell RNA ed Immunoistochimica - Elisa); il restante materiale è stato inviato per effettuare l esame istologico.
In accordo ai dati della letteratura, i valori medi sierici dei tre parametri da noi considerati, nonchè quelli ricavati dalle biopsie della cavità uterina di donne con carcinoma, sono significativamente più elevati rispetto a quelli di donne con patologie benigne dell endometrio ed ancora di più rispetto ai controlli. La MMP-9 e il suo inibitore TIMP-1, hanno mostrato lo stesso andamento di OPN anche se i valori di TIMP-1 circolante, in accordo con i dati riferiti in letteratura hanno mostrato una maggiore correlazione rispetto alla MMP-9.
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Cubo, Abert Montserrat. "Estadificación prequirúrgica del carcinoma endometrial mediante ecografía en dos y tres dimensiones." Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/672056.
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Objectius: El nostre objectiu era comparar el rendiment diagnòstic de l’ecografia transvaginal (ETV) i la ressonància magnètica (RM) per predir la profunditat de la invasió miometrial (IMP) i la invasió estromal cervical (IEC) en pacients amb càncer d’endometri (CE).
Mètodes: Estudi prospectiu i consecutiu que inclou totes les pacients amb CE diagnosticades entre l’octubre del 2013 i el juliol del 2018 a l’Hospital Vall d’Hebron de Barcelona. Es va realitzar una estadificació preoperatòria amb ETV i ressonància magnètica seguida d’una estadificació quirúrgica. La histologia final es va considerar com a estàndard de referència. Es van calcular la sensibilitat, l’especificitat, les raons de verosimilitut i la precisió diagnòstica per a les dues tècniques d’imatge per a la predicció de la IMP i la IEC. Es va calcular l’índex d’acord. Es van utilitzar les directrius STARD 2015.
Resultats: Es van incloure un total de 177 pacients consecutivament. La sensibilitat va ser major per a ETV en comparació amb la ressonància magnètica, tant per a la predicció de IMP (68% (95% IC 55-79) enfront del 60% (95% IC 47-72), respectivament) com de IEC (49% (95% CI 35- 62) contra el 29% (IC del 95% 18-43), respectivament). Les especificitats van ser similars per a la predicció de IMP (ETV 84% (95% CI 77-90) i ressonància magnètica 92% (95% CI 85-96)) i iguals per a IEC (95% (95% CI 90-98). L’índex d’acord entre ETV i RN va ser de 0,74 per a IMP i 0,99 per a IEC.
Conclusions: El rendiment diagnòstic de la ETV no és inferior a la ressonància magnètica per a la predicció de IMP i IEC en el carcinoma endometrial i pot tenir un paper com a tècnica d’imatge de primera línia en l’avaluació preoperatòria del càncer d’endometri.Objetivos: Nuestro objetivo fue comparar el rendimiento diagnóstico de la ecografía transvaginal (ETV) y la resonancia magnética (RM) para predecir la profundidad de la invasión del miometrio (IMP) y la invasión del estroma cervical (IEC) en pacientes con cáncer de endometrio (CE). Métodos: Estudio prospectivo y consecutivo que incluye todas las pacientes con CE diagnosticadas entre octubre de 2013 y julio de 2018 en el Hospital Vall d’Hebron de Barcelona. La estadificación preoperatoria se realizó con ETV y RM seguida de estadificación quirúrgica. La histología final se consideró como estándar de referencia. Se calcularon la sensibilidad, la especificidad, las razones de probabilidad y la precisión diagnóstica para ambas técnicas de imagen para la predicción de IMP y IEC. Se calculó el índice de concordancia. Se utilizaron las pautas STARD 2015. Resultados: Se incluyeron un total de 177 pacientes de forma consecutiva. La sensibilidad fue mayor para ETV en comparación con RM tanto para la predicción de IMP (68% (95% CI 55-79) versus 60% (95% CI 47-72), respectivamente) como para la predicción de IEC (49% (95% CI 35- 62) versus 29% (IC 95% 18-43), respectivamente). Las especificidades fueron similares para la predicción de IMP (ETV 84% (95% CI 77-90) y ETV 92% (95% CI 85-96)) e iguales para IEC (95% (95% CI 90-98). El índice de acuerdo entre ETV y RM fue 0,74 para IMP y 0,99 para IEC. Conclusiones: El rendimiento diagnóstico de ETV no es inferior a la RM para la predicción de IMP y la IEC en el carcinoma de endometrio y puede desempeñar un papel como técnica de imagen de primera línea en la evaluación preoperatoria del cáncer de endometrio.
Objectives: We aimed to compare the diagnostic performance of transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) to predict the depth of myometrial invasion (DMI) and cervical stromal invasion (CSI) in patients with endometrial cancer (EC). Methods: Prospective and consecutive study including all EC diagnosed between October 2013 and July 2018 at the Vall d’Hebron Hospital in Barcelona. Preoperative staging was performed with TVUS and MRI followed by surgical staging. Final histology was considered as the reference standard. Sensitivity, specificity, likelihood ratios and diagnostic accuracy were calculated for both imaging techniques for the prediction of DMI and CSI. Agreement index was calculated. The STARD 2015 guidelines were used. Results: A total of 177 patients were consecutively included. Sensitivity was higher for TVUS compared to MRI both for the prediction of DMI (68% (95%CI 55-79) versus 60% (95%CI 47-72), respectively) and CSI (49% (95%CI 35-62) versus 29% (95%CI 18-43), respectively). Specificities were similar for the prediction of DMI (TVUS 84% (95%CI 77-90) and MRI 92% (95%CI 85-96)) and equal for CSI (95% (95%CI 90-98). The agreement index between TVUS and MRI was 0.74 for DMI and 0.99 for CSI. Conclusions: The diagnostic performance of TVUS is not inferior to MRI for the prediction of DMI and CSI in EC and can play a role as a first line imaging technique in the preoperative evaluation of endometrial cancer.
Universitat Autònoma de Barcelona. Programa de Doctorat en Pediatria, Obstetrícia i Ginecologia
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Sorolla, Bardají Anabel. "Estudi del proteasoma i altres dianes terapèutiques en el melanoma i el carcinoma d’endometri." Doctoral thesis, Universitat de Lleida, 2012. http://hdl.handle.net/10803/83625.
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Donada la resistència a la quimioteràpia que presenta el melanoma i el carcinoma d’endometri avançat, és important la investigació destinada a buscar dianes terapèutiques. En aquest treball hem investigat els efectes de d’anàlegs de la somatostatina (SA), d’inhibidors del proteasoma (PI) com Bortezomib, de l’inhibidor de receptors tirosina cinasa Sunitinib i la combinació de Sunitinib i Bortezomib en línies cel•lulars de melanoma. Aquesta combinació també l’hem testat en el carcinoma d’endometri. S’observa que les cel•lules de melanoma expressen varis receptors de la somatostatina. Els PI són eficients a l’hora d’induir una parada en el cicle cel•lular i apoptosi. Les línies cel•lulars que presenten PDGFRα i VEGFR2 són sensibles a Sunitinib, i aquest interacciona amb Bortezomib de forma sinèrgica. En el carcinoma d’endometri, Sunitinib indueix una parada en el cicle cel•lular, apoptosi, inhibeix la via NFκB i interacciona sinèrgicament amb Bortezomib. Els SAs i PI podrien ser útils en combinació amb altres agents i l’ús de Bortezomib i Sunitinib ha mostrat ser efectiu en determinats casos de melanoma i en el carcinoma d’endometri.Dada la resistencia a la quimioterapia que presenta el melanoma y el carcinoma de endometrio avanzado, es importante aquella investigación destinada a buscar dianas terapéuticas. En este trabajo hemos investigado los efectos de análogos de la somatostatina (SAs), de inhibidores del proteasoma (PI) como Bortezomib, del inhibidor de receptores tirosina cinasa Sunitinib y la combinación de Sunitinib y Bortezomib en líneas celulares de melanoma. Esta combinación también la hemos testado en el carcinoma de endometrio. Se observa que las células de melanoma expresan varios receptores de la somatostatina. Los PI son eficientes a la hora de inducir una parada en el ciclo celular y apoptosis. Las líneas celulares que presentan PDGFR α i VEGFR2 son sensibles a Sunitinib, y éste interacciona con Bortezomib de forma sinérgica. En el carcinoma de endometrio, Sunitinib induce una parada en el ciclo celular, apoptosis, inhibe la via NFκB e interacciona sinérgicamente con Bortezomib. Los SAs y PI podrían ser útiles en combinación con otros agentes y el uso de Bortezomib y Sunitinib ha demostrado ser efectivo en determinados casos de melanoma y en el carcinoma de endometrio.
As advanced melanoma and endometrial carcinoma is highly resistant to chemotherapy it is important the research focused to the search of therapeutic targets. In the present work, we have investigated the effects of somatostatin analogues (SAs), proteasome inhibitors (PI) such as Bortezomib, the tyrosine kinase receptor inhibitor Sunitinib and the combined therapy of Sunitinib and Bortezomib. This combination has been also tested in endometrial carcinoma. It is observed that melanoma cell lines express various somatostatin receptors. In addition, proteasome inhibitors induce a cell cycle arrest and apoptosis. Those cells presenting activated PDGFRα or VEGFR2 are more sensitive to Sunitinib and this interacts synergistically with Bortezomib. In endometrial carcinoma, Sunitinib induces a cell cycle arrest, apoptosis, inhibits NFκB pathway and interacts synergistically with Bortezomib. The SAs and PI could be useful combined with other agents and the use of Bortezomib and Sunitinib has shown to be effective in certain cases of melanoma and in endometrial carcinoma.
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Muñoz, Menéndez Ana Belén. "Resonancia magnética nuclear y marcadores moleculares en el estudio prequirúrgico de pacientes con carcinoma de endometrio. Correlación con el estadio quirúrgico final." Doctoral thesis, Universidad de Cantabria, 2014. http://hdl.handle.net/10803/133095.
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En general, se acepta el uso de la Resonancia preoperatoria para el estadiaje en el carcinoma de endometrio. Sin embargo, en nuestro hospital, hemos venido observando una cierta discrepancia entre los resultados de la Resonancia Magnética prequirúrgica y el estadiaje quirúrgico posterior. Esto nos ha hecho preguntarnos si podríamos, incluso, tener que plantearnos si es, en nuestro medio, una prueba diagnóstica necesaria en todas nuestras pacientes como diagnóstico previo a la cirugía, o si, tal vez, deberíamos excluirla de nuestro protocolo de estadiaje del cáncer de endometrio. Se estudiaron las historias de las pacientes con cáncer endometrial que fueron operadas en nuestro servicio entre Enero de 2007 y Diciembre de 2011, a las cuales se les había realizado una Resonancia Magnética previa a la cirugía. Tan solo se registró coincidencia completa entre los resultados de la Resonancia Magnética Nuclear prequirúrgica y el estadio quirúrgico final en el 47.2% de los casos analizados. Los datos obtenidos en el subgrupo de los carcinomas endometriales tipo I resultan mucho más razonables, observando un 63.9% de estadiaje correcto, más acorde a los estudios publicados sobre el tema, además de que en ningún caso de este subgrupo un fallo en la estadificación significó un cambio en el tratamiento final ni en el pronóstico.In general , the use of preoperative magnetic imaging is accepted for staging in endometrial carcinoma. However, in our hospital, we have been observing a discrepancy between the results of preoperative MRI and subsequent surgical staging . This has made us wonder if, in our environment, it is a necessary diagnostic test in all our patients for diagnosis prior to surgery , or if , perhaps , we should exclude it from our endometrial cancer staging protocol. We studied the patients with endometrial cancer who had surgery in our department between January 2007 and December 2011, which had undergone preoperative MRI. There was a complete coincidence between the results of the Nuclear Magnetic Resonance preoperative and final surgical stage only in 47.2 % of cases analyzed. The data obtained in the subgroup of type I endometrial carcinomas are much more reasonable, seeing a 63.9 % correct staging , more in line with published studies on the topic, and in any case of this subgroup, staging failure meant a change in the final treatment or prognosis.
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Dahmoun, Marju. "Apoptosis, proliferation, and sex steroid receptors in endometrium and endometrial carcinoma." Doctoral thesis, Umeå : Univ, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-112.
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Vaskivuo, T. (Tommi). "Regulation of apoptosis in the female reproductive system." Doctoral thesis, University of Oulu, 2002. http://urn.fi/urn:isbn:9514266676.
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Abstract
Apoptosis is a genetically programmed mechanism for a multicellular organism to remove cells that are unnecessary, or potentially harmful. The female reproductive system is characterised by a high rate of cellular proliferation. At the same time, apoptosis is also abundant during the normal physiological function of the ovary and endometrium. More than half of the 7 million oocytes that are produced during human ovarian development are deleted before birth and only about 400 oocytes reach the stage of ovulation during the female fertile lifespan. The fate of the non-ovulatory follicles is atresia, occurring through the mechanism of apoptosis. The endometrium goes through radical renewal processes during each menstrual cycle. Apoptosis has been suggested to participate in the regulation of endometrial cellular homeostasis. Errors in this mechanism can result in endometrial diseases such as hyperplasia and cancer. In this work, apoptosis and its regulation were studied in the human fetal and adult ovary, normal endometrium and endometrial pathologies.
In fetal ovaries, apoptosis was already abundantly present in oocytes at 13 weeks of gestation. The maximum rate of apoptosis was seen between the 14th and 20th weeks, after which apoptosis decreased towards term. Ovarian Bcl-2 expression was detected in early fetal life during weeks 13 and 14. Bax expression was observed throughout the studied period, from week 13 to 40. The expression of transcription factor GATA-4, which is linked to follicular survival, was localised to the granulosa cells and was high in early fetal life and decreased somewhat towards term. In adult life apoptosis was located in the granulosa cells of the growing follicles. In ovarian biopsies from women homozygous for the inactivating C566T mutation of the FSH receptor, apoptosis or GATA-4 expression was not detected. During corpus luteum regression a peak in apoptosis was detected 10 - 12 days after the LH surge, and was preceded by an increase in 17HSD type 1 and TNF-α expression. During normal menstrual cycles, the highest rate of apoptosis was observed in the menstrual endometrium. This increase in apoptosis was preceded by a decreased Bcl-2/Bax ratio. In endometrial hyperplasia, the rate of apoptosis was similar to that seen during normal proliferation of the endometrium, but an apparent increase was observed in grade II endometrial carcinoma. In grade III carcinoma, the rate of apoptosis was lower than in grade II carcinoma but higher than in hyperplasia.
These results indicate that apoptosis is the mechanism behind the substantial oocyte demise during ovarian development. During adult life, apoptosis was mainly localised to the granulosa cells of the growing follicles which do not reach the stage of a dominant follicle. In ovaries where FSH action is abolished, folliculogenesis was impaired and ovarian apoptosis was negligible. Apoptosis is also the underlying mechanism of corpus luteum regression. In the endometrium, apoptosis has a role in rejuvenating the endometrium for growth during the next endometrial cycle and in regulating cellular homeostasis.
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HAMID, ATIA AKHTAR. "Cyclical Change of hMSH2 Protein Expression in Normal endometrium during the Menstrual Cycle and its Overexpression in Endometrial Hyperplasia and Sporadic Endometrial Carcinoma." Kyoto University, 2002. http://hdl.handle.net/2433/149704.
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Kyoto University (京都大学)0048
新制・課程博士
博士(医学)
甲第9461号
医博第2474号
新制||医||795(附属図書館)
UT51-2002-G219
京都大学大学院医学研究科外科系器官外科学(婦人科学産科学)専攻
(主査)教授 中畑 龍俊, 教授 丹羽 太貫, 教授 藤井 信吾
学位規則第4条第1項該当
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TOZZI, ALESSANDRA. "The unfolded protein response: a link between endometrioid ovarian carcinoma and endometriosis." Doctoral thesis, Università Politecnica delle Marche, 2017. http://hdl.handle.net/11566/245358.
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Lo scopo del seguente lavoro è di analizzare il profilo di attivazione dei geni legati al pathway dell’Unfolded Protein Response (UPR) nel carcinoma endometrioide dell’ovaio e di valutare il suo possibile coinvolgimento nella trasformazione neoplastica dell’endometriosi.
Lo studio è stato eseguito utilizzando diversi campioni istologici: carcinoma endometrioide dell’ovaio, tessuto ovarico sano, cisti endometriosica, endometrio eutopico provenienti da pazienti con endometriosi e da pazienti con endometrio sano. Da tutti i campioni è stato estratto l’RNA e sintetizzato il cDNA utilizzando la trascrizione inversa. Il cDNA è stato utilizzato per i saggi di espressione quantitativa dei geni, tramite Real Time PCR, con analisi dei geni appartenenti al pathway dell’UPR. I campioni sono stati divisi in tre gruppi: patienti con endometriosi (n=6), pazienti sane (n=6) e pazienti con carcinoma endometrioide dell’ovaio (n=6).
L’analisi statistica effettuata è il t-test, con analisi delle differenze statistiche tra i dati provenienti da pazienti sane (CTRL) e pazienti affette da endometriosi (Ectopic e Eutopic) e pazienti affette da carcinoma endometrioide dell’ovaio (CA).
Abbiamo in primo luogo analizzato la differente espressione del pathway dell’UPR nel carcinoma endometrioide dell’ovaio, comparandolo al tessuto ovarico sano e abbiamo dimostrato un’alterata espressione dei geni dell’UPR nelle pazienti tumorali. In secondo luogo, abbiamo analizzato l’espressione genica dell’UPR nel carcionma endometrioide ovarico, comparandola all’endometrio sano di pazienti sane e di pazienti affette da endometriosi.
Il nostro studio mostra una graduale riduzione dell’espressione del gene XBP1 nell’endometriosi, caratterizzata da intensa infiammazione e nel carcinoma endometrioide dell’ovaio, valorizzando l’ipotesi che XBP1 possa rappresentare un marker di trasformazione neoplastica.
In conclusione XBP1 ha un’alta espressione nell’endometrio sano, un tessuto costitutivamente secretivo, e poi gradualmente riduce la sua espressione nell’endometriosi e, in maniera più accentuata, nel carcinoma ovarico.
Comprendere questi meccanismi potrebbe rappresentare uno step importante per una migliore definizione della patogenesi tumorale e per lo sviluppo in futuro di terapie geniche mirate.The present study aims to analyze the activation profile of Unfolded Protein Response (UPR) related genes in endometriod ovarian carcinoma and to assess its possible involvement in the neoplastic transformation from endometriosis. The study was performed using different histological samples: endometrioid carcinoma of the ovary, healthy ovary, endometriosis cysts, eutopic endometrium from patients with endometriosis and healthy endometrium. From all the samples RNA was extracted and cDNA synthesis was performed by reverse transcription. cDNA was used for quantitative gene expression assays, made by Real Time PCR, analyzing genes belonging to the UPR pathway. Samples were divided into three groups: patients with endometriosis (n = 6), healthy patients (n = 6) patients with ovarian endometrioid carcinoma (n = 6). Statistical analysis performed was a t - test, testing the statistical differences, between data means from healthy patients (CTRL) and groups of patients with endometriosis (Ectopic and Eutopic) and patient with endometrioid carcinoma of the ovary (CA). We started analyzing the different expression of UPR pathway in endometrioid ovarian carcinoma compared to healthy ovary and we demonstrated an altered UPR gene expression in patients affected by endometrioid ovarian carcinoma, compared to healthy ovary. As a second step, we decided to analyze the UPR pathway genetic expression in the endometrioid ovarian carcinoma compared to the endometrium of healthy patients and of endometriosis patients. Our study shows a gradual reduction of XBP1 expression in endometriosis, characterized by intense inflammation, and endometrioid ovarian carcinoma, thus strengthening the hypothesis of XBP1 as a marker of neoplastic transformation. Conclusively XBP1s has a high basic expression in healthy endometrium, being a secretive tissue, then gradually decreases in endometriosis and to a higher degree, in ovarian carcinoma. Understanding these mechanisms could represent an important step, for a better definition of cancer pathogenesis, and also in the future, for the development of customized therapies.
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Pandey, Vijay. "Secreted oncogenes in endometrial carcinoma." Thesis, University of Auckland, 2010. http://hdl.handle.net/2292/8195.
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Endometrial carcinoma is the most common malignancy of the female reproductive tract and the incidence in developed countries is rising. Poor survival of late stage and recurrent endometrial carcinoma patients, particularly with an aggressive histologic subtype, necessitate the development of new therapeutic modalities for advanced stage and recurrent endometrial carcinoma. Recent published data have demonstrated elevated levels of human growth hormone (hGH) in endometriosis and endometrial adenocarcinoma. Herein, I demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in endometrial carcinoma cell lines RL95-2 and AN3 resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH expression in endometrial carcinoma cells promoted anchorage-independent growth and increased cell migration/invasion in vitro. In a xenograft model of human endometrial carcinoma, autocrine hGH enhanced tumor size and progression. Changes in endometrial carcinoma cell gene expression stimulated by autocrine hGH was consistent with the altered in vitro and in vivo behavior. Functional antagonism of hGH in wild-type RL95-2 cells significantly reduced cell proliferation, cell survival, and anchorage- independent cell growth. These studies demonstrate a functional role for autocrine hGH in the development and progression of endometrial carcinoma and indicate potential therapeutic relevance of hGH antagonism in the treatment of endometrial carcinoma. I further provided evidence for the functional role of the neurotrophic factor artemin (ARTN) in progression of endometrial carcinoma. Increased ARTN protein expression was observed in endometrial carcinoma and ARTN protein expression in endometrial carcinoma was significantly associated with higher tumor grade and invasiveness. Forced expression of ARTN in endometrial carcinoma cells significantly increased total cell number as a result of enhanced cell cycle progression and cell survival. In addition, forced expression of ARTN significantly enhanced anchorage-independent growth and invasiveness of endometrial carcinoma cells. Moreover, forced expression of ARTN increased tumor size in xenograft models and produced highly proliferative, poorly differentiated and invasive tumors. The ARTN stimulated increases in oncogenicity and invasion were mediated by increased expression and activity of AKT1. siRNA mediated depletion or antibody inhibition of ARTN significantly reduced oncogenicity and invasion of endometrial carcinoma cells. Thus, inhibition of ARTN may be considered as a potential therapeutic strategy to retard progression of endometrial carcinoma. Furthermore, I demonstrated that ARTN stimulates the oncogenicity and invasiveness of endometrial carcinoma cells. Herein, I demonstrate that ARTN modulates the sensitivity of endometrial carcinoma cells to agents used to treat latestage endometrial carcinoma. Forced expression of ARTN in endometrial carcinoma cells decreased sensitivity to doxorubicin and paclitaxel. Accordingly, depletion of ARTN by small interfering RNA or functional inhibition of ARTN with antibodies significantly increased sensitivity of endometrial carcinoma cells to doxorubicin and paclitaxel. Forced expression of ARTN in endometrial carcinoma cells abrogated doxorubicininduced G2-M arrest and paclitaxel-induced apoptosis. ARTN increased CD24 expression in endometrial carcinoma cells by transcriptional up-regulation, and CD24 was partially correlated to ARTN expression in endometrial carcinoma. Forced expression of CD24 in endometrial carcinoma cells stimulated cell proliferation and oncogenicity, enhanced cell invasion, and decreased sensitivity to doxorubicin and paclitaxel. Depletion of CD24 in endometrial carcinoma cells abrogated ARTNstimulated resistance to doxorubicin and paclitaxel. ARTN-stimulated resistance to doxorubicin and paclitaxel in endometrial carcinoma cells is therefore mediated by the specific regulation of CD24. Functional inhibition of ARTN may therefore be considered as an adjuvant therapeutic approach to improve the response of endometrial carcinoma to specific chemotherapeutic agents.
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Ngai, Yin-ping. "p21-activated kinases in endometrial carcinoma." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40738528.
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魏燕萍 and Yin-ping Ngai. "p21-activated kinases in endometrial carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40738528.
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Saidi, Samir Arif. "A systems biology approach to endometrial carcinoma." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612981.
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Wang, Yue. "Molecular analysis of mitochondrial DNA alterations in endometrial carcinomas." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B32059127.
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Lundgren, Caroline. "Endometrial carcinoma : prognostic factors and protein expression profiling /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-002-8/.
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Levan, Kristina. "Molecular characterization of type 1 endometrial carcinomas /." Göteborg : Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, 2009. http://hdl.handle.net/2077/19401.
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Liao, Xiaoyun. "Hedgehog signaling pathway and epigenetic studies in ovarian carcinomas and endometrial carcinomas." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41290367.
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Liao, Xiaoyun, and 廖晓耘. "Hedgehog signaling pathway and epigenetic studies in ovarian carcinomas and endometrial carcinomas." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290367.
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Chan, Kwan-yi Queeny, and 陳君怡. "Molecular study of pi-class glutathione-S-transferase in endometrial carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29157717.
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Wang, Yue, and 王悦. "Molecular analysis of mitochondrial DNA alterations in endometrial carcinomas." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B32059127.
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Boman, Karin. "Endometrial carcinoma : steroid hormones and receptors in relation to proliferation." Doctoral thesis, Umeå universitet, Onkologi, 1993. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100588.
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The significance of the hormonal milieu for endometrial changes is as well-known as its link with endometrial carcinoma. Unopposed oestradiol treatment is shown to increase the incidence for this cancer. Obesity leads to elevated levels of oestrogens and is a risk factor for endometrial carcinoma. An association between high tumour proliferation and prognosis is a general feature of human cancer. Tumour growth can be expressed as proliferation rate and flow cytometry (FCM) is a sensitive and reproducable method to estimate S-phase fraction (SPF) and ploidy level. Both parameters have been shown to correlate with prognosis. Sex steroid hormone levels were analysed together with clinical parameters, SPF, and receptors in established endometrial carcinoma. The study consisted of postmenopausal women with endometrial adenocarcinoma. H ormones were analysed in 127 patients, 99 were analysed for FCM and 60 for oestrogen and progesterone receptors. RIA technique was used for hormone assay of oestrone, oestradiol, progesterone, androstenedione and testosterone plasma levels. The receptors were analysed with an immunohistochemical method, and SPF and ploidy level by flow cytometry. A wide range of oestrogen concentrations was found. Some patients had levels comparable to fertile women. Strong correlations were found between body mass index, weight and depth of uterine cavity. No relations were found between receptors and SPF, apart from oestrogen- receptor positive tumours having a lower SPF when compared with receptor negative tumours. The influence of oestradiol on tumour proliferation expressed as SPF was ambiguous. SPF was increased with higher oestradiol levels in the group of peri-diploid, well-differentiated tumours, while a negative correlation was found for the peri-diploid, moderately differentiated tumours. The aneuploid and poorly differentiated tumours had a high SPF regardless of oestradiol concentration. The association between progesterone concentration and SPF was of a more general nature. Progesterone above a threshold level was related to a lower SPF in well-differentiated and moderately differentiated tumours. Thus endogenous progesterone seems to play a role in controlling the tumour’s proliferation activity, in contrast to oestradiol, that had a role which did not appear to relate to proliferation activity in any specific direction. The only stimulative association was seen in well-differentiated tumours, but SPF was still below the mean value for all diploid tumours.Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 5 uppsatser.
digitalisering@umu
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Koivisto, Christopher Steven. "Dissecting the Pathogenesis of Type I Endometrial Carcinoma through Mouse Models." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1531995361428894.
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Wei, Linxuan, Xiaolin Liu, Wenjing Zhang, Yuyan Wei, Yingwei Li, Qing Zhang, Ruifen Dong, et al. "Overexpression and oncogenic function of HMGA2 in endometrial serous carcinogenesis." E-CENTURY PUBLISHING CORP, 2016. http://hdl.handle.net/10150/614759.
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The high-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor highly expressed in fetal tissue and malignant tumors but rarely detected within normal adult tissues. The clinical implications and biological functions of HMGA2 in endometrial carcinoma are largely unknown. Here we report that HMGA2 expression was barely detected in benign endometrium samples (2 of 28 samples). However, HMGA2 expression increased significantly from precancerous lesion endometrial glandular dysplasia (7 of 17, 41.2%), to serous endometrial intraepithelial carcinoma (5 of 8, 62.5%) and to full blown endometrial serous carcinoma (39 of 59, 66.1%). Functional characterization of HMGA2 revealed that the gene has both tumor growth promotion and metastasis. In addition, HMGA2 induced epithelial-mesenchymal transition (EMT) through modulation vimentin and β-catenin. Furthermore, HMGA2 overexpression started from endometrial serous precancers, non-invasive cancers, as well as in full blown carcinomas in a p53 knockout mouse model we recently established in our laboratory. Our findings suggest that HMGA2 may serve as a useful diagnostic marker in the assessment of endometrial serous cancer and its precursor lesions.
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Ayakannu, Thangesweran. "Investigation of endocannabinoid system signalling pathways and their regulations in endometrial carcinoma." Thesis, University of Leicester, 2017. http://hdl.handle.net/2381/39387.
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In the UK, endometrial cancer (EC) is the 4th most common cancer and its incidence is rapidly rising. This study aimed to elucidate the role of the endocannabinoid system (ECS) in the pathogenesis of EC. Plasma and endometrial tissues levels of anandamide (AEA), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) quantified by UHPLC from atrophic and EC group. Using the qRT-PCR and immunohistochemistry (IHC), CB1, CB2, FAAH, NAPE-PLD, GPR55 and TRPV1, mRNAs and protein levels was evaluated, respectively. The effects of in-vitro exposure of Ishikawa cell-line to AEA, OEA, PEA and capsaicin were evaluated. Plasma and tissue AEA levels were significantly (p<0.05) higher in EC than control, as were PEA levels. Logistic regression raised the area under the ROC curve (AUC) from 0.781 for plasma AEA, 0.857 for PEA and 0.543 for OEA to a combined AUC of 0.933 for EC diagnosis. The transcript level of FAAH was 75% lower in EC and NAPE-PLD levels were more variable. Histomorphometric analysis of FAAH and NAPE-PLD staining complements the transcript data. CB1 and CB2 mRNA were significantly decreased by 90% (p< 0·0004) and 80% (p< 0·0001), respectively, compared with control and these was supported by the IHC. In the EC, GPR55 mRNA were significantly raised (p<0.0020) compared with control and its protein expressions were markedly stained in EC tissues. TRPV1 receptor transcript levels were significantly reduced (p<0.0054) in EC compared with controls and markedly decreased in EC by IHC. Cancer cell growth in-vitro was decreased by the endocannabinoids in a pseudo dose-dependent and time-dependent manner. The endocannabinoids might prevent cancer cell growth by inhibiting cell proliferation or by activating apoptosis. This idea was tested using BAX/Bcl-2 and Ki-67 expression and found to be due to decrease cell proliferation. It is evident that there is an apparent perturbation of ECS at tissue and plasma levels and this could be used as diagnostic and prognostic markers with potential therapeutic target for the prevention EC.
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Kurata, Yasuhisa. "Diagnostic performance of MR imaging findings and quantitative values in the differentiation of seromucinous borderline tumour from endometriosis-related malignant ovarian tumour." Kyoto University, 2018. http://hdl.handle.net/2433/232129.
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Dann, James MacBeth. "Regulation of Vascular Endothelial Growth Factor in endometrial cancer cells by food compounds." Thesis, University of Canterbury. School of Biological Sciences, 2008. http://hdl.handle.net/10092/2113.
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Endometrial cancer is one of the most significant gynaecological malignancies that affect women from New Zealand and the rest of the world. One of the critical stages in the development of a tumour is the onset of hypoxia. The malignancy responds by having raised levels of Hypoxia Inducible Factor (HIF) that in turn induces increased production of Vascular Endothelial Growth Factor (VEGF). VEGF is a potent angiogenic factor that will mediate vascular supply of nutrients and oxygen to the developing tumour. The aim of this study was to investigate whether two compounds found in extracts of plant materials, Resveratrol (Resveratrol) and Epigallocatechin gallate (EGCG), altered the levels of VEGF in the supernatant of cultured endometrial cancer cells. Resveratrol is a phytoalexin that is found in many foods, such as grapes, nuts and berries, as well as in high concentrations in some red wines. 100 µM of resveratrol was added to cell cultures for 24 hours. VEGF levels in the supernatant were then analysed using ELISA. Resveratrol was found to have significant inhibitory effects in both primary endometrial cancer cell cultures and immortalised endometrial cancer cell cultures. Resveratrol was also shown to reverse the increase in VEGF caused by the hypoxia mimic cobalt chloride (CoCl₂). Epigallocatechin gallate (EGCG) is an antioxidant catechin extracted from green tea. The effect of EGCG was analysed using the same method as for resveratrol. 100 µM of EGCG was also shown to have a significant inhibitory effect on the level of VEGF in the supernatant of cultured endometrial cancer cells, as well as reducing the effect of CoCl₂. These results suggest that selected food compounds, resveratrol and EGCG, can reduce VEGF levels by inhibiting HIF. Further investigation This may have anti-tumour effects in women with endometrial cancer.
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Kuwahara, Ryo. "A Predictor of Tumor Recurrence in Patients With Endometrial Carcinoma After Complete Resection of the Tumor: The Role of Pretreatment Apparent Diffusion Coefficient." Kyoto University, 2020. http://hdl.handle.net/2433/253483.
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Wong, Sze-yin Shirley. "Single nucleotide polymorphism in follicle stimulating hormone receptor and the development of endometrial carcinoma." Click to view the E-thesis via HKUTO, 2002. http://sunzi.lib.hku.hk/hkuto/record/B31971349.
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Wong, Sze-yin Shirley, and 黃思賢. "Single nucleotide polymorphism in follicle stimulating hormone receptor and the development of endometrial carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31971349.
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Tonon, Ângela Favorito Santarém. "Claudina-3 e Claudina- 4, potenciais marcadores de agressividade no carcinoma endometrial Tipo I /." Botucatu, 2013. http://hdl.handle.net/11449/108608.
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Orientador: Paulo TraimanCoorientador: Maria Aparecida Custódio Domingues
Banca: Agnaldo Lopes da Silva Filho
Banca: Spergio Mancini Nicolau
Banca: Wagner José Gonçalves
Resumo: O Carcinoma de Endométrio é a neoplasia epitelial maligna que acomete mulheres no pré, pós e peri -menopausa. Segundo diferenças endócrinas, metabólicas, fatores de risco e morfologia é classificado em dois grandes grupos: Tipo I (endometrióide) e Tipo II (não endometrióide). O Tipo I perfaz 90 % dos carcinomas de endométrio e sua patogenia esta ligada a exposição excessiva ao estrógeno. O Tipo II é incomum, com fatores predisponentes menos conhecidos. O sintoma mais relevante do carcinoma de endométrio é o sangramento pós-menopausa. Seu diagnóstico é feito pela comprovação histológica, associada aos exames de imagem e laboratoriais. Seu tratamento é fundamentalmente cirúrgico. O fator prognóstico mais importante é a presença ou ausência de metástase nos linfonodos regionais. Atualmente, buscam-se marcadores biológicos e teciduais que indiquem pior prognóstico. Este trabalho verificou a imunoexpressão da claudina-3 (CLDN3) e claudina-4 (CLDN4) nos carcinomas de endométrio Tipo I e Tipo II, relacionando-as com endométrio proliferativo e atrófico, aspectos clínicos, anatomopatológicos, perfil hormonal, índice de proliferação celular e expressão da p53, na tentativa de estabelecer a importância destas proteínas na progressão e agressividade tumoral e o seu valor prognóstico. Foram estudados 79 casos de carcinoma de endométrio e comparados com 74 endométrios normais. Avaliou-se a imunoexpressão das CLDNs 3 e 4, receptor estrogênico, receptor de progesterona, índice de proliferação celular (Ki67) e p53, pela técnica de imunoistoquímica. Observou-se que o padrão de coloração da membrana para CLDN3 se mostrou difuso nos carcinomas, quando comparado com os endométrios normais que exibiu padrão focal. O número de células marcadas com CLDN3 estava diminuído nos carcinomas Tipo I, porém com intensidade aumentada. Nesta análise foi possível verificar que ...
Abstract: Carcinoma of the Endometrium is a malignant epithelial tumor which affects pre, peri and post-menopausal women. It is classified into two major groups, according to endocrine, metabolic risk factors and morphological differences: Type I (endometrioid) and Type II (non-endometrioid). Type I accounts for 90% of all endometrial carcinomas and its pathogenesis is linked to excessive estrogen exposure. The Type II is less common, with poorly defined predisposing factors. The most important symptom of endometrial carcinoma is postmenopausal bleeding. Diagnosis is achieved through histological evidence, in association with imaging and laboratorial exams. Treatment is primarily surgical. The most important prognostic factor is the presence or absence of metastases in regional lymph nodes. Bio and tissue markers that indicate worse prognosis are the focus of current research. This study examined the immunoexpression of claudin-3 (CLDN3) and claudin-4 (CLDN4) in endometrial carcinomas Type I and Type II, and their relation to proliferative and atrophic endometrium, clinical and pathological features, hormonal status, proliferation index and p53 expression, in an attempt to establish the importance of these proteins in tumor progression and aggressiveness and their prognostic value. Seventy-nine cases of endometrial carcinoma were studied and compared with 74 normal endometria. The immunoexpression of CLDNs 3 and 4, estrogen receptor, progesterone receptor, cell proliferation index (Ki67) and p53 were all evaluated by immunohistochemistry. Observation verified that the pattern of membrane staining for CLDN3 was diffuse in carcinomas compared with normal endometrium which presented a focal pattern. The number of cells stained with CLDN3 was lower in Type I carcinomas, while staining intensity was greater. Analysis verified that 25% of cases with high expression of CLDN4 and Ki-67 developed metastasis, while 33% of cases with greater CLDN4 staining ...
Mestre
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De, Leo Antonio <1985>. "Integrated molecular analysis of endometrial carcinoma: translation of biomarker profiles into the clinical practice." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amsdottorato.unibo.it/9642/1/de%20leo_antonio_tesi.pdf.
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The Cancer Genome Atlas (TCGA) collaborative project identified four distinct prognostic groups of endometrial carcinoma (EC) based on molecular alterations: (i) the ultramutated subtype that encompassed POLE mutated (POLE) cases; (ii) the hypermutated subtype, characterized by MisMatch Repair deficiency (MMRd); (iii) the copy-number high subtype, with p53 abnormal/mutated features (p53abn); (iv) the copy-number low subtype, known as No Specific Molecular Profile (NSMP). Although the prognostic value of TCGA molecular classification, NSMP tumors present a wide variability in molecular alterations and biological aggressiveness. This study aims to investigate the impact of ARID1A and CTNNB1/β-catenin alterations by targeted Next-generation sequencing (NGS) and immunohistochemistry (IHC) in a consecutive series of 125 molecularly classified ECs. NGS and IHC were used to assign surrogate TCGA groups and to identify molecular alterations of multiple target genes including POLE, PTEN, ARID1A, CTNNB1, TP53. Associations with clinicopathologic parameters, molecular subtypes, and outcomes identified NSMP category as the most heterogeneous group in terms of clinicopathologic features and outcome. Integration of surrogate TCGA molecular classification with ARID1A and β-catenin analysis showed NSMP cases with ARID1A mutation characterized by the worst outcome with early recurrence, while NSMP tumors with ARID1A wild-type and β-catenin alteration had indolent clinicopathologic features and no recurrence. This study indicates how the identification of ARID1A and β-catenin alterations in EC represents a simple and effective way to characterize NSMP tumor aggressiveness and metastatic potential.
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Choma, André. "Etude rétrospective sur les carcinomes de l'endomètre : expérience clinique d'un groupe coopératif alésien." Montpellier 1, 1989. http://www.theses.fr/1989MON11305.
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Ebeid, Kareem Atef Nassar. "Nanoparticles for targeted treatment of cancer." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6567.
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Cancer is the second leading cause of death in the USA, following cardiovascular disease. Treating cancer using conventional therapies is associated with low response rates and high toxicity, because these therapies usually lack specific tumor accumulation. Loading anticancer drugs into intelligently designed polymeric nanoparticles (NPs) can serve in delivering these drugs specifically to the tumor site, thus boosting their efficacy and reducing any associated off target toxicity. Targeting NPs to the tumor site can occur through either passive or active means. In passive targeting, NPs of specific size and surface characteristics can exploit the tumor’s erratic vasculature and occluded lymphatic drainage to extravasate the systemic circulation and accumulate preferentially at the tumor site. Active targeting mandates grafting the surface of NPs with a ligand that specifically interacts with a protein expressed at higher levels at the tumor site, in comparison to elsewhere in the body. In the current research, we independently investigated the utilization of passive and active targeting strategies to treat aggressive forms of cancer.
Initially, passively targeted poly(lactic-co-glycolic acid) (PLGA) NPs to treat aggressive forms of endometrial cancer (EC) were investigated. A novel combination of soluble paclitaxel (PTX), a first line chemotherapy for EC, and soluble BIBF1120 (BIBF, nintedanib), an antiangiogenic molecular inhibitor, was first tested against three EC cell lines bearing different p53 mutations. The results showed that only EC cells with loss of function (LOF) p53 were sensitive to the combination therapy, indicating the potential of this combination to engender synthetic lethality to PTX. Next, NPs loaded with PTX were investigated with respect to the impact of varying the polymer lactic acid to glycolic acid ratio and the surfactant type on the major physicochemical properties of the prepared nanoparticles, drug loading, cellular uptake, cytotoxicity, and drug release. The optimum formulation was then loaded with BIBF and the combination of independently loaded passively targeted NPs were further evaluated for in vivo activity against a xenograft model of LOF p53 EC. The combination of independently loaded NPs exhibited the highest reduction in tumor volume and prolonged survival when compared to soluble PTX, PTX NPs or untreated control. These data highlight this specific combination of NPs as a novel promising therapy for LOF p53 EC.
In a second study, the use of actively targeted NPs to treat liver cancer was explored. In this study, a combination of small interfering RNA (siRNA) against astrocyte elevated gene-1 (AEG-1), and all-trans retinoic acid (ATRA) was investigated as a new therapy for hepatocellular carcinoma (HCC). AEG-1 is a highly expressed oncogene that is directly involved in HCC progression and aggressiveness, in addition to reducing the ability of retinoic acid to induce apoptosis in HCC cells. First, a new conjugate was synthesized that was capable of delivering siRNA selectively to HCC cells, using galactose as a targeting moiety. The conjugate was prepared by linking poly(amidoamine) (PAMAM) dendrimers, polyethylene glycol (PEG) and lactobionic acid (Gal, disaccharide containing galactose) (PAMAM-PEG-Gal). We confirmed the synthesis of the conjugate using 1H-NMR, Mass spectrometry and Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry. Next, nanoplexes of the synthesized conjugate, PAMAM-PEG-Gal, and AEG-1 siRNA were prepared. Nanoplexes were further characterized for their size, surface charge, morphology, and electrophoretic mobility to identify the optimum complexation ratio between PAMAM-PEG-Gal and the siRNA. Then, mice bearing orthotopic luciferase expressing HCC cells were treated with the optimum nanoplex formulation. Results showed that a combination of AEG-1 nanoplexes and ATRA results in a significant reduction in luciferase expression, reduced liver weight, lower AEG-1 mRNA levels and increased apoptosis, when compared to utilizing nanoplexes with silencing control (siCon), siCon+ATRA, or AEG-1 nanoplexes alone. The results indicate that the combination of liver-targeted AEG-1 nanoplexes and ATRA may be a potential treatment for aggressive HCC.
These data place targeted NPs as a promising efficient delivery system for cancer treatment.
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Llobet, Navàs David. "Estudi dels mecanismes moleculars implicats en la sensibilització a l'apoptosi en cèl·lules de carcinoma d'endometri." Doctoral thesis, Universitat de Lleida, 2009. http://hdl.handle.net/10803/8097.
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Wang, Lin 1967. "A comparative study using endovaginal sonography and magnetic resonance imaging in the staging of endometrial carcinoma /." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32895.
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Introduction. Most patients with early-stage endometrial carcinoma are treated with hysterectomy. The knowledge of the stage of disease could impact greatly on the eventual therapeutic decision. Numerous studies have investigated the use of endovaginal ultrasonography (US) and magnetic resonance (MR) imaging in the preoperative staging of endometrial carcinoma. Although a number of studies have demonstrated no significant difference in the accuracy of MR imaging and endovaginal US in assessing myometrial invasion, more recently, dynamic contrast-enhanced MR imaging has been found to be significantly superior to the non-enhanced T2-weighted MR imaging in the preoperative evaluation of endometrial carcinoma.Purpose. (1) To evaluate prospectively the relative accuracy of endovaginal US (including Doppler) and MR imaging using phased array pelvic multicoil in the preoperative staging of endometrial carcinoma with histopathological correlation on the same patient population, (2) To determine whether the addition of contrast-enhanced MR sequences to high resolution fast spinecho (FSE) T2-weighted sequences, can improve the diagnostic accuracy of staging endometrial carcinoma. (Abstract shortened by UMI.)
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Garcia, Tiago Selbach. "Avaliação da concordância histológica entre a amostra endometrial pré-operatória e a peça uterina nos carcinomas do endométrio." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/139987.
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Base teórica: o tratamento do carcinoma endometrial é feito através do estadiamento cirúrgico, que envolve histerectomia com salpingo-oforectomia bilateral e linfadenectomia pélvica e para-aórtica. Questiona-se o benefício da linfadenectomia sistemática em todos os pacientes, já que o risco de disseminação linfática em tumores de baixo risco é pequeno e não há evidências de benefício terapêutico em sua realização. Desse modo, tentam-se encontrar modos de determinar, na avaliação pré-operatória, quais são os pacientes que poderão se beneficiar da linfadenectomia e aqueles que podem prescindir do procedimento. Objetivos: avaliar a concordância da avaliação anatomopatológica entre a amostra endometrial pré-operatória e a peça cirúrgica das pacientes submetidas a tratamento cirúrgico primário do carcinoma de endométrio, correlacionando com características das pacientes e das amostras da patologia. Métodos: foram incluídos pacientes submetidos a tratamento cirúrgico para carcinoma de endométrio que tinham diagnóstico pré-operatório através de amostragem endometrial. Os prontuários foram revisados e as amostras disponíveis na instituição foram procuradas para posterior releitura por dois patologistas cegados para as demais informações anatomopatológicas. Resultados: foram incluídos 166 pacientes, com uma idade média de 64,6 anos. Das biópsias, 118 eram tumores endometrioides, 38 não-endometrioides e as demais, hiperplasia. As taxas de concordância foram de 93,2% para tumores endometrioides e 68,9% para não-endometrioides, com um índice kappa (k) de 0,73 para o tipo histológico. O grau tumoral distribui-se na amostra como G1 em 37,1%, G2 em 35,7% e G3 em 27,1%, com uma taxa de concordância de 61,5%, 56% e 78,9%, respectivamente, e k=0,46. Dos tumores G1, somente 1,9% teve upgrade para G3, em comparação com 16% das lesões G2. Não houve diferença estatística na taxa de concordância do tipo histológico e grau tumoral em função do local de execução da biópsia, método de amostragem e intervalo biópsia-cirurgia. Biópsias com pés > 3g tiveram uma concordância do grau tumoral significativamente melhor (p=0,040). Amostras de 105 pacientes estavam disponíveis no HCPA e foram reavaliadas por dois patologistas, com uma taxa de concordância interobservador geral de 73,3% (k=0,58) para o tipo histológico e 57,9% (k=0,54) para o grau tumoral. Conclusão: a acurácia da biópsia pré-operatória em predizer as características da peça cirúrgica não é ideal. Deve-se ter cuidado ao utilizar essa informação para determinar a extensão da cirurgia a ser realizada, sob risco de ser realizado subestadiamento. Estas baixas taxas de concordância correlacionam-se também com as baixas taxas de concordância interobservador. Novos sistemas de graduação e equipes de especialistas são possibilidades para melhorar esta questão.Background: endometrial carcinoma treatment is based on surgical staging, including hysterectomy with bilateral salpingo-oophorectomy and pelvic and paraortic lymphadenectomy. The benefits of systematic lymphadenectomy in all patients have been questioned, since the risk of dissemination in low risk tumors is small and there is no evidence of benefits in its execution. Thereby, researches are looking for ways to determine, by preoperative evaluation, which patient will benefit from full staging and those who can do without the procedure. Objectives: evaluate the agreement between the preoperative endometrial samples and the surgical specimens in endometrial carcinoma, correlating it with characteristics of the samples and patients included, and evaluate the interobserver agreement of the preoperative biopsy. Methods: patients submitted to surgery as primary treatment for endometrial carcinoma at HCPA with a preoperative endometrial sampling were included. Their medical charts were reviewed. The available samples of the preoperative biopsies were recollected for reanalyzes by two pathologists. Inadequate transcriptions of the biopsy report were excluded. Results: we included 166 patients, with a mean age of 64.6 years. Of the biopsies, 118 were endometrioid, 38 were non-endometrioid and the remaining, hyperplasia. The agreement rates were 93.2% for endometrioid tumors and 68.9% for non-endometrioid, with a kappa index of 0.73 for the tumor cell type. The tumor FIGO grade distributed as G1 in 37.1%, G2 in 35.7% and G3 in 27.1%, with an agreement rate of 61.5%, 56% and 78.9%, respectively. The general kappa index for FIGO grading was 0.46. Of the G1 tumors, only 1.9% upgraded to G3, while 16% of the G2 lesions upgraded. There was no statistical difference in the agreement rates of tumor cell type and FIGO grading in function of place of biopsy execution, method of endometrial sampling and biopsy-surgery interval. Biopsies weighing more than 3g had a significantly better agreement in FIGO grading (p=0.040). Samples of 105 were available at HCPA and were reevaluated by 2 pathologists, with a general interobserver agreement 73.3/% (k=0.58) for tumor cell type and 57.9% (k=0.54) for grading. Conclusion: the accuracy of the preoperative biopsy in predicting the definite surgical characteristics it is not ideal. Caution must be taken when using this information to determine the surgical extension, due to the risk of under staging. These low rates of agreement are correlated with the low interobserver agreement. New grading systems and specialists teams are possible ways of improving this issue.
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Taylor, Sarah Elizabeth. "Investigation of Protein Phosphatase 2A A-alpha Subunit Mutation as a Disease Driver in High-Grade Endometrial Carcinoma." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1567791544641051.
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Sandberg, Therese, and Rebecka Fridén. "Utbyte av xylen till Tissue Clear som avparaffineringsmedel vid diagnostik av endometrioid carcinom med DNA-ploidi." Thesis, Hälsohögskolan, Jönköping University, HHJ, Avd. för naturvetenskap och biomedicin, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-48782.
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Flödescytometrisk analys av DNA-ploiditeten används vid diagnostisering av endometriecancer. DNA-ploidi reflekterar cellcykeln och avgör om tumörens cellpopulationen är diploid eller aneuploid, där aneuploiditet förknippas med sämre prognos. Vid analys av paraffininbäddat vävnadsmaterial används avparaffineringsmedlet xylen, vars toxiska egenskaper försämrar arbetsmiljön på laboratoriet. Den har en stark och obehaglig lukt som kan orsaka illamående och yrsel. Syftet med studien var att undersöka om xylen kan ersättas med xylensubstitutet Tissue Clear, ett isoparaffinskt kolväte som är mindre toxiskt. Studien omfattade paraffininbäddad humanvävnad från endometrioid carcinom (n=20), både diploid (n=15) och aneuploid (n=5) vävnad, som avparaffinerades med xylen respektive Tissue Clear innan DNA-ploidi utfördes. Eventuella skillnader inom de flödescytometriska parametrarna % CV-diploid, % S-fas, % debris och DI-aneuploid undersöktes och vid statistisk analys kunde ingen signifikant skillnad ses på samtliga parametrar. Eftersom analysen utförs sällan i rutin är antalet prover i studien relativt stor, trots att detta kan anses vara en liten kvantitet. Av dessa var endast 25 % av proverna aneuploida. Att en patient uppvisar aneuploiditet är ovanligt och därför ansågs även denna mängd som tillräckligt stor. Studien visar att avparaffinering med Tissue Clear är ekvivalent med xylen och därmed kan Tissue Clear ersätta xylen oavsett om vävnaden är diploid eller aneuploid.DNA ploidy is used for endometrial cancer diagnosis. It reflects the cell cycle and determines whether the cell population in tumors is diploid or aneuploid. When analyzing paraffin embedded tissues xylene can be used for deparaffinization, whose toxicity impairs the laboratory´s work environment. Its strong and unpleasant smell can cause nausea and dizziness. The aim of this study was to investigate if xylene can be replaced with Tissue Clear, an isoparaffinic hydrocarbon that is less toxic. The study included paraffin embedded human tissues from endometrioid carcinoma (n=20), both diploid (n=15) and aneuploid (n=5), deparaffinized with xylene or Tissue Clear before DNA ploidy was performed. Potential differences between the parameters % CV-diploid, % S-phase, % debris and DI-aneuploid were statistically examined and showed no significant differences. The sample amount in this study might be considered low, though it is relatively high since the analysis is rarely performed routinely. Among these only 25 % were aneuploid. Patients showing aneuploidy is rare and the amount was therefore considered to be sufficient as well. The study shows that deparaffinization with Tissue Clear generates equivalent results as for xylene and can thereby replace xylene regardless if the tissue is diploid or aneuploid.
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Lindberg, Mallory E. "THE IMPACT OF E-CADHERIN AND PHOSPHATASE AND TENSIN HOMOLOG ABLATION IN THE UTERUS: THE PROGRESSION OF TYPE I ENDOMETRIAL CARCINOMA." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/theses/1411.
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E-&ndashcadherin (CDH1) is a cell adhesion molecule that coordinates key morphogenetic processes regulating cell growth, cell proliferation and apoptosis. Loss of CDH1 is a trademark of the cellular event epithelial to mesenchymal transition (EMT), which increases the metastatic potential of malignant cells. PTEN is a tumor suppressor gene commonly mutated in many human cancers, including endometrial cancer. In the mouse uterus, ablation of Pten induces epithelial hyperplasia, leading to endometrial carcinomas. However, loss of Pten alone does not affect longevity until around 5 months. Similarly, conditional ablation of Cdh1 alone does not predispose mice to cancer. We characterized the impact of dual Cdh1 and Pten ablation using Pgr-Cre (Cdh1d/d Ptend/d) in the mouse uterus. We observed that Cdh1d/d Ptend/d mice died at postnatal day 15-&ndash19 with massive blood loss from their reproductive tract (abnormal metrorrhagia) with prevalent vascularization in both the endometrium and myometrium. Their uteri were abnormally structured with curly horns, disorganized epithelial structure, and increased cell proliferation. Co-&ndashimmunostaining of KRT8 and ACTA2 showed invasion of epithelial cells into the myometrium. Further, the uteri of Cdh1d/d Ptend/d mice had prevalent vascularization in both the endometrium and myometrium. We also observed reduced expression of estrogen and progesterone receptors, loss of cell adherens and tight junction molecules (CTNNB1 and claudin), as well as activation of AKT in the uteri of Cdh1d/d Ptend/d mice. However, complex hyperplasia was not found in the uteri of Cdh1d/d Ptend/d. Collectively, these findings suggest that ablation of Pten with Cdh1 in the uterus accelerates cellular invasiveness and angiogenesis, and causes early death. Thus, this model does not allow sufficient time for the emergence of advanced, clinically over aggressive endometrial tumorigenesis and metastasis. Additionally, we looked at a new Cre system to ablate Pten and Cdh1 only in the epithelial cells of the uterus. Sprr2f, an estrogen dependent gene that is found highly expressed in the uterus, helps with structure and barrier function of epithelial cells. Prg-Cre turns on at postnatal day 3-5 before development of the uterus; whereas, Sprr2f-Cre is active around 3 weeks which is after uterine development. We have driven the ablation of Cdh1d/d Ptend/d using the Sprr2f-Cre. The Sprr2f-Cre Cdh1d/d Ptend/d mice successfully lived to 2 months. The Sprr2f-Cre Ptend/d mice displayed hyperplastic epithelial cells, most prominently in the glandular like structures of the uterus. Lack of cellular structure was observed in the Sprr2f-Cre Cdh1d/d Ptend/d mice. We also developed a model of orthotopic tumor transplantation to study further tumor development including cell invasion, dissemination and metastasis. The uteri of control, Cdhd/d, Ptend/d and Cdhd/d Ptend/d mice were collected and dissected to approximately ~1 mm in diameter. Then, the tissue fragments were orthotopically implanted into the uterine wall (endometrium) of wild-type syngeneic host mice. We have observed successful implantation and sustainability of the tissue through this technique. The tissue viability was successfully verified by implanting donor uterine pieces under the kidney capsule of recipient wild type mice. This study has shown that the ablation of Cdh1 and Pten in the mouse uterus initiates a more aggressive form of type I endometrial carcinoma when using Pgr-Cre as well as Sprr2f-Cre. However, neither conditional ablation approaches allowed us to fully observe the progression of the carcinoma to a metastatic disease. Our intrauterine endometrial/myometrial implantation technique proved to be an incomplete method to further study the metastatic potential of the PgrCre/+ Cdh1f/f Ptenf/f mice.
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Honkavuori-Toivola, M. (Maria). "The prognostic role of matrix metalloproteinase-2 and -9 and their tissue inhibitor-1 and -2 in endometrial carcinoma." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526204505.
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Abstract Endometrial carcinoma is the most common gynegologic malignancy in developed countries. Due to early symptoms, including abnormal uterine bleeding, endometrial cancer is often diagnosed at an early stage and in that case usually has a good prognosis and high cure rates. However, the nature of the disease is heterogeneous. During the last decades, the improvement in survival rates among endometrial cancer patients has not been significant, suggesting that the traditional clinicopathological factors may be inadequate to identify patients with high-risk disease. Furthermore, aggressive adjuvant treatments can be costly and very toxic. Therefore, better prognostic markers associated with biological aggressiveness of endometrial carcinoma are needed to identify the patients with high-risk disease, and to be able to select the treatment more individually. Gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) have been found to play a role in tumor progression. In the present work, the expression and prognostic value of MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed in endometrial carcinoma. The patient material consisted of a total of 266 women diagnosed with primary endometrial carcinoma. The tissue expression of immunoreactive proteins was examined in paraffin-embedded tumor sections by immunohistochemical staining using specific antibodies, and the pretreatment serum levels of the proteins were quantitatively measured by ELISA. Tissue MMP-2 expression associated with a worsened prognosis, whereas tissue TIMP-2 overexpression was an indicator of a favorable outcome. Furthermore, we observed a combination of strong MMP-2 and weak TIMP-2 tissue expression to identify a group of women at high risk of adverse outcome in endometrial carcinoma. Patients with negative MMP-2 immunostaining had the best prognosis, regardless of TIMP-2 staining result. In serum measurements, high preoperative TIMP-1 concentration was a prognostic indicator of unfavorable outcome. These results indicate that tissue MMP-2 and TIMP-2 as well as circulating TIMP-1 may be prognostic markers in endometrial carcinoma. Of these, tissue MMP-2 seems to be the most potent prognostic marker. Studies with larger patient materials are needed to further explore the value of these enzymes in clinical practice in endometrial cancerTiivistelmä Kohdunrungon syöpä on yleisin gynekologinen maligniteetti kehittyneissä maissa. Varhaisten oireiden, kuten poikkeavan verisen vuodon, vuoksi kohdunrungon syöpä havaitaan usein varhaisessa vaiheessa, jolloin sen ennuste on hyvä. Taudin käyttäytyminen voi kuitenkin olla moninaista. Viime vuosikymmenten aikana kohdunrungon syöpään sairastuneiden ennuste ei ole merkittävästi parantunut. Vaikuttaisi siltä, että perinteiset ennustetekijät eivät ole riittävän tarkkoja ennustamaan syövän taudinkulkua. Lisäksi liitännäishoidot voivat olla kalliita, ja niihin voi liittyä vakavia haittavaikutuksia. Uusien biologisten ennustetekijöiden löytäminen olisi tärkeää, jotta aggressiivista syöpätyyppiä sairastavat potilaat pystyttäisiin tunnistamaan entistä paremmin, ja hoito kyettäisiin räätälöimään yksilöllisemmin taudinkuvaa vastaavasti. Gelatinaasien (MMP-2 ja MMP-9) sekä niiden kudosinhibiittoreiden (TIMP-1 ja TIMP-2) on havaittu osallistuvan syövän etenemiseen. Tässä tutkimuksessa tarkasteltiin MMP-2:n ja MMP-9:n sekä niiden kudosinhibiittoreiden TIMP-1:n ja TIMP-2:n ilmentymistä ja ennusteellista merkitystä kohdunrungon syövässä. Aineisto käsitti yhteensä 266 primaariseen kohdunrungon syöpään sairastunutta naista. Määritysmenetelminä käytettiin sekä immunohistokemiallista värjäystä parafiiniin valettujen kudosnäytteiden osalta että ELISA-määrityksiä ennen hoitoa otettujen seeruminäytteiden osalta. Syöpäkudoksen runsas MMP-2 -proteiinin ilmentyminen liittyi epäsuotuisaan ennusteeseen, kun taas kasvainkudoksen voimakas TIMP-2 -proteiinin ilmentyminen oli hyvän ennusteen merkki. Lisäksi kasvainkudoksen voimakkaan MMP-2- ja heikon TIMP-2 -proteiinien ilmentymisen yhdistelmän havaittiin liittyvän suurempaan syövästä johtuvaan kuolleisuuteen. MMP-2 -negatiivisten potilaiden eloonjäämisennuste oli paras, TIMP-2 -värjäystuloksesta riippumatta. Seerumin korkea TIMP-1 -pitoisuus oli merkittävä huonontuneen ennusteen merkki. Tutkimuksen tulokset viittaavat siihen, että kasvainkudoksessa esiintyvät MMP-2- ja TIMP-2 -proteiinit samoin kuin seerumin TIMP-1 -pitoisuus voivat ennustaa kohdunrungon syövän kliinistä käyttäytymistä. Kasvainkudoksessa esiintyvä MMP-2 -proteiini vaikuttaisi olevan merkittävin ennusteellinen tekijä, mutta tulosten varmistamiseksi tarvitaan lisää tutkimuksia suuremmilla potilasaineistoilla
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Kanopienė, Daiva. "Clinical relevance of studies on microsatellite instability and DNA mismatch repair system protein expression in endometrial carcinomas." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20141209_111951-10166.
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The evaluation of microsatellite instability in cancer patients might be of clinical importance as a prognostic and predictor factor. The aim of this study − evaluate the frequency and status of microsatellite instability and DNA mismatch repair protein expression in endometrial cancer and to relate the obtained results to clinicopathologic characteristics as well as patient survival. This study enrolled 109 patients.The objectives of the study: to determine the frequency and status of microsatellite instability by using two marker panels (earlier created BAT-25, BAT-26, NR-21, NR-24, MONO-27 and a new BAT-52, BAT-55, BAT-56, BAT-57, BAT-59 panels) recommended by Promega Corporation (USA); to compare the frequency and status of microsatellite instability with tumor clinicopathologic characteristics; to investigate the expression of DNA mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) in tumors with high-frequency microsatellite instability; to evaluate the impact of microsatellite instability on the survival of patients. The results showed that high-frequency microsatellite instability was detected two times more frequently with the new panel of markers in comparison while using earlier created panel. A statistically significant difference regarding tumor grade and myometrial invasion was found between the groups with high-frequency microsatellite instability and stable phenotype. There was no association between the survival of patients and microsatellite instability.Mikrosatelitų nestabilumo tyrimai svarbūs vėžio ligos prognozei vertinti bei parenkant individualų gydymą. Darbo tikslas − ištirti mikrosatelitų nestabilumo dažnį, pobūdį ir klaidingai suporuotų nukleotidų DNR pažaidų taisymo sistemos baltymų raišką sergant gimdos kūno vėžiu ir gautus rezultatus susieti su pacienčių klinikinėmis-patologinėmis charakteristikomis bei jų išgyvenamumu. Į stebėsenos perspektyvinį tyrimą buvo įtrauktos 109 pacientės. Darbo uždaviniai: nustatyti mikrosatelitų nestabilumo dažnį ir pobūdį tarp sergančiųjų gimdos kūno vėžiu, panaudojus Promega Corporation (JAV) sukurtus du žymenų rinkinius (anksčiau sukurtą BAT-25, BAT-26, NR-21, NR-24, MONO-27 ir naująjį BAT-52, BAT-55, BAT-56, BAT-57, BAT-59); palyginti mikrosatelitų nestabilumo dažnį ir pobūdį su pacienčių klinikinėmis-patologinėmis charakteristikomis; ištirti DNR pažaidų taisymo sistemos baltymų (MLH1, PMS2, MSH2, MSH6) raišką gimdos kūno navikuose, kuriuose nustatytas didelio dažnio mikrosatelitų nestabilumas; įvertinti mikrosatelitų nestabilumo įtaką pacienčių išgyvenamumui. Tyrimų rezultatai parodė, kad mikrosatelitų didelio dažnio nestabilumas dvigubai dažniau nustatytas naudojant naująjį žymenų rinkinį, palyginti su anksčiau sukurtu žymenų rinkiniu. Statistiškai reikšminga sąsaja konstatuota tarp mikrosatelitų didelio dažnio nestabilumo arba jo nebuvimo ir naviko diferenciacijos laipsnio bei invazijos į miometriumą gylio. Sergančiųjų išgyvenamumas nebuvo susijęs su mikrosatelitų nestabilumu. ... [toliau žr. visą tekstą]
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Appel, Márcia. "CA 125 e p53 no pré-operatório da neoplasia de endométrio e seu valor preditivo para doença linfonodal." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/97253.
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Introdução: o carcinoma de endométrio é uma das neoplasias ginecológicas mais comuns nos países industrializados. O tratamento desta doença é primariamente cirúrgico. Segundo a normatização da Federação Internacional de Ginecologia e Obstetrícia (FIGO), a cirurgia ideal consiste na realização de histerectomia total, anexectomia bilateral, linfadenectomia retroperitonial e coleta de citologia peritoneal. No entanto, a realização sistemática da linfadenectomia tem sido contestada. Alguns centros de referência acreditam que deva ser realizada apenas em um grupo de pacientes com alto risco para disseminação linfática da doença. O desafio é encontrar marcadores pré-operatórios que possam ser preditivos da presença de doença linfonodal e, assim , virem a ser utilizados para a definição da necessidade da linfadenectomia. Objetivos: verificar se a expressão imuno-histoquímica (IMH) positiva da p53 na amostra endometrial diagnóstica e, se o valor sérico do CA 125 obtido no tempo pré-operatório, podem ser efetivos para prever a presença de doença linfonodal. Métodos: um estudo transversal restrospectivo foi realizado. Foram incluídas 111 pacientes com carcinoma de endométrio submetidas a histerectomia com anexectomia bilateral e linfadenectomia com ou sem citologia peritoneal. Noventa pacientes apresentavam CA 125 pré-operatório e 73, a avaliação da p53. Cinquenta e quatro pacientes apresentavam as duas variáveis em combinação. Foram estabelecidas as associações entre o valor de CA 125 e da expressão IMH da p53 com o envolvimento linfonodal. Uma curva ROC foi construída para identificar o valor de CA 125 com melhor Sensibilidade (S) e Especificidade (E) para doença linfonodal.Introduction: endometrial carcinoma is one of the most common gynecological malignancies in industrialized countries. The treatment of this disease is primarily surgical. According to the International Federation of Gynecology and Obstetrics surgery ideal consists in performing total hysterectomy, bilateral adnexectomy, retroperitoneal lymphadenectomy and peritoneal cytology. However, the systematic lymphadenectomy has been disputed, and should only be performed in a group of patients at high risk of lymphatic spread of the disease. The challenge is to find preoperative markers that may be predictive of the presence of lymph node disease and thus come to be used to determine the necessity of lymphadenectomy. Objectives: to determine whether the positive immunohistochemical expression (IMH) of p53 in diagnostic endometrial sample and, if the value of serum CA 125, obtained during pre-operative, can be effective to predict the presence of lymph node disease. Methods: a cross-sectional study was conducted. The final sample consisted of 111 patients with endometrial carcinoma undergoing hysterectomy with bilateral adnexectomy and lymphadenectomy with or without peritoneal cytology. Ninety two patients had preoperative CA 125 and 73, evaluation of p53. Fifty four patients had both variables in combination. Associations have been established between the value of CA 125 and IMH expression of p53 with lymph node involvement. A ROC curve was constructed to identify the value of CA 125 with better sensitivity (S) and specificity (E) for lymph node disease.
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Santos, Nataly Melo dos. "Análise do perfil de expressão e papel fisiopatológico de isoformas da p53 e da osteopontina em linhagens celulares de carcinoma de endométrio." Niterói, 2017. https://app.uff.br/riuff/handle/1/3785.
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Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.
Uma série de genes vem sendo estudados por terem sua expressão aberrante em tumores de endométrio. Dentre eles, a osteopontina (OPN) e a p53, os quais são expressos de forma aberrante no carcinoma de endométrio (CE). Tem sido demonstrado que a expressão da OPN é capaz de regular a expressão de p53 e vice-versa. No entanto, ainda não há dados sobre as isoformas destes produtos gênicos e suas possíveis relações no CE. Este trabalho teve por objetivo avaliar o perfil de expressão e o potencial papel fisiopatológico das isoformas da OPN e da p53 em distintas linhagens celulares de endométrio. A expressão destes alvos foi avaliada por PCR em tempo real, imunoblot e imunofluorescência. Observamos que a OPNa é a isoforma predominante dentre as três isoformas, tanto em linhagens tumorais quanto não tumorais de endométrio. No entanto, apenas a isoforma OPNc apresenta expressão diferencial entre linhagens tumorais e uma não tumoral. De forma similar, todas as isoformas de p53 também são expressas nestas linhagens investigadas, sendo a p53 completa a isoforma predominante em linhagens tumorais e a Δ40p53 a segunda mais expressa, em especial em linhagens representativas de tumores do Tipo I. A variante Δ40p53 apresenta expressão predominante em linhagens celulares não tumorais de endométrio. Em conjunto, estes dados evidenciam correlação entre a expressão predominante da isoforma OPNa e a variante completa da p53, com padrões específicos de expressão da OPNc e da Δ40p53, de acordo as linhagens analisadas. Estes achados abrem perspectivas da potencial aplicação de isoformas variantes da OPN e de p53 enquanto biomarcadores no diagnóstico diferencial e também para avaliação prognóstica em tumores de endométrio.
Several genes have been studied by being overexpressed in endometrial tumors. Among them, osteopontin (OPN) and p53, which are overexpressed in endometrial carcinoma (EC). It has been demonstrated that the expression of OPN can regulate the expression of p53 and vice-versa. However, data is lacking regarding these gene products and their putative associations in EC. This work aims to evaluate the expression profile and the potential physiopathological roles of OPN and p53 isoforms in distinct endometrial cell lines.The expression of these gene targets has been evaluated here by real time PCR, immunoblot and immunofluorescense. We observed that OPNa is the predominant isoform among those three tested, both in tumor and non-tumoral cell lines. However, only OPNc isoform is differentially expressed between tumor and non-tumoral cell lines. Similarly, all p53 isoforms are expressed in these tested cell lines, being the full lenght p53 the predominant isoform in tumor cell lines, while Δ40p53 is the second variant in expression levels, especially in cell lines that are representative of Type I tumors. The Δ40p53 variant has predominat expression in non-tumoral cell lines. As a whole, these data evidence correlation between the predominant expression of OPNa and the full lenght p53 variant, with specific expression patterns observed for OPNc and Δ40p53, according to analyzed cell lines. These data open perspectives of the potential use of OPN and p53 isoform variants as biomarkers for differential diagnosis and prognostic evaluation in endometrial tumors.
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Reinhold, Caroline. "The use of endovaginal sonography and Doppler ultrasound in the detection of endometrial carcinoma in women presenting with postmenopausal bleeding." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ64436.pdf.
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Silveira, Razyane Audibert. "Avaliação da concordância da expressão imuno-histoquímica da proteína p53 entre a amostra endometrial pré-operatória e a peça uterina nos carcinomas de endométrio." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/179704.
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Objetivo: avaliar a concordância da expressão imuno-histoquímica (IMH) da proteína p53 (p53) na amostra endometrial e na peça cirúrgica de histerectomia, associando-a a fatores como tipo histológico, grau tumoral e estadiamento, bem como analisar a concordância interobservador para expressão e intensidade de expressão da p53 entre biópsia diagnóstica e peça cirúrgica. Métodos: estudo transversal retrospectivo, no qual foram incluídas pacientes com carcinoma endometrial submetidas à biópsia de endométrio e tratamento cirúrgico primário na Unidade de Oncologia Genital do HCPA. As lâminas foram lidas por dois patologistas. O percentual de expressão da p53 foi avaliado em três categorias (<10%, 10-50% e >50%). A intensidade foi avaliada como fraca, média ou forte. Foram extraídos dados do prontuário eletrônico das pacientes. A concordância foi avaliada através do coeficiente Kappa ponderado. Resultados: 72 pacientes foram incluídas, com idade média de 65,5 anos. O percentual de expressão da p53 entre biópsia e peça cirúrgica apresentou uma taxa de concordância de 70,8%, com um índice de Kappa ponderado de 0,64 e a intensidade de expressão apresentou uma taxa de concordância de 69,4%, com Kappa ponderado de 0,65. A avaliação da concordância do percentual de expressão da p53 conforme tipo histológico e grau tumoral apresentou coeficientes de Kappa ponderado de 0,64 e 0,72, nos carcinomas não endometrioides e G3, respectivamente. Tais dados, com diferença estatística significativa. A concordância interobservador para a expressão e intensidade da p53 na biópsia apresentou índices de Kappa 9 ponderado de 0,77 e 0,75, respectivamente. Na peça cirúrgica, os índices de kappa ponderado foram de 0,85 e 0,88, para a expressão e intensidade, respectivamente. Conclusões: as taxas de concordância para a expressão e intensidade de expressão IMH da p53 entre biópsia endometrial e peça cirúrgica foram boas, podendo ser útil em tempo pré-operatório, para a seleção de pacientes candidatas a uma cirurgia mais extensa, principalmente quando os dados anatomopatológicos da biópsia forem insuficientes para tal decisão. Devemos, no entanto, levar em consideração que existem muitos outros marcadores moleculares para a neoplasia endometrial, sendo provável futuramente o estudo da concordância deles em associação ao da p53.Objective: To evaluate the agreement of the immunohistochemical (IMH) expression of the p53 protein (p53) in preoperative endometrial tissues and in surgical specimens obtained during hysterectomy, to determine the association of this agreement with factors such as histological type, tumor grade and stage and to evaluate interobserver agreement for the expression and intensity of p53 between the diagnostic biopsy and the surgical specimen. Methods: Retrospective cross-sectional study. Patients with endometrial carcinoma who submitted to endometrial biopsy and primary surgical treatment at the HCPA Genital Oncology Unit were included. The slides were assessed by two pathologists. The percentage of p53 expression was evaluated and categorized into one of three groups (<10%, 10-50% and >50%). The intensity was evaluated as weak, medium or strong. The agreement was assessed by the weighted Kappa coefficient. Results: 72 patients with a mean age of 65.5 years were included. The percentage of p53 expression between the biopsy and the surgical specimen presented an agreement rate of 70.8%, with a weighted Kappa index of 0.64. The intensity of expression had an agreement rate of 69.4% with a weighted Kappa of 0.65. When evaluated according to histological type and tumor grade, the agreement for p53 expression showed weighted Kappa indexes of 0.64 and 0.72 in non-endometrioid and G3 carcinomas, respectively (p<0.001). With respect to the biopsy, the interobserver agreement for the expression and intensity of p53 had weighted Kappa indexes of 0.77 and 0.75, respectively. With respect to the surgical specimen, the weighted Kappa indexes were 0.85 and 0.88 for expression and intensity, respectively. 11 Conclusions: This study found good agreement rates for the expression and intensity of p53 IMH expression between the endometrial biopsy specimen and the surgical specimen, which may be useful in a preoperative setting for the selection of patients who are candidates for more extensive surgery, especially when anatomopathological biopsy data are insufficient for such a decision.
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Rush, Craig M. "Characterization of MAX and FOXA2 mutations unique to endometrial cancer." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1542204873523922.
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Nanbu, Kanako. "Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas : correlation with clinicopathology, sex steroid receptor status, and p53 protein expression." Kyoto University, 1999. http://hdl.handle.net/2433/181231.
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Butler, Stephen Andrew. "Investigations into the role of human chorionic gonadotrophin beta as a new growth factor in carcinoma of the bladder, cervix and endometrium : novel structures, functions and treatments." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249591.
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