Статті в журналах: "High-grade serous ovarian carcinoma"

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Casey, Laura, and Naveena Singh. "Ovarian High-Grade Serous Carcinoma." Surgical Pathology Clinics 12, no. 2 (June 2019): 515–28. http://dx.doi.org/10.1016/j.path.2019.01.007.

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Pannu, Harpreet K., Weining Ma, Emily Craig Zabor, Chaya S. Moskowitz, Richard R. Barakat, and Hedvig Hricak. "Enhancement of Ovarian Malignancy on Clinical Contrast Enhanced MRI Studies." ISRN Obstetrics and Gynecology 2013 (February 13, 2013): 1–8. http://dx.doi.org/10.1155/2013/979345.

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Purpose. To assess if there is a significant difference in enhancement of high grade serous carcinoma of the ovary compared with other ovarian malignancies on clinically performed contrast enhanced MRI studies. Methods. In this institutional-review–board-approved study, two radiologists reviewed contrast enhanced MRI scans in 37 patients with ovarian cancer. Readers measured the signal intensity (SI) of ovarian mass and gluteal fat pre- and postcontrast administration. Percentage enhancement (PE) was calculated as [(post-pre)/precontrast SI] × 100. Results. Pathology revealed 19 patients with unilateral and 18 patients with bilateral malignancies for a total of 55 malignant ovaries-high grade serous carcinoma in 25/55 ovaries (45%), other epithelial carcinomas in 12 ovaries (22%), nonepithelial cancers in 8 ovaries (14%), and borderline tumors in 10 ovaries (18%). Enhancement of high grade serous carcinoma was not significantly different from other invasive ovarian malignancies (Reader 1 ; Reader 2 ). Enhancement of invasive ovarian malignancies was more than borderline tumors but did not reach statistical significance (Reader 1; Reader 2 ). Conclusion. On clinically performed contrast enhanced MRI studies, enhancement of high grade serous ovarian carcinoma is not significantly different from other ovarian malignancies.

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Kshirsagar, Malti, Wei Jiang, and Ie-Ming Shih. "DNA Damage Response is Prominent in Ovarian High-Grade Serous Carcinomas, Especially Those with Rsf-1 (HBXAP) Overexpression." Journal of Oncology 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/621685.

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DNA damage commonly occurs in cancer cells as a result of endogenous and tumor microenvironmental stress. In this study, we applied immunohistochemistry to study the expression of phosphorylated Chk2 (pChk2), a surrogate marker of the DNA damage response, in high grade and low grade of ovarian serous carcinoma. A phospho-specific antibody specific for threonine 68 of Chk2 was used for immunohistochemistry on a total of 292 ovarian carcinoma tissues including 250 high-grade and 42 low-grade serous carcinomas. Immunostaining intensity was correlated with clinicopathological features. We found that there was a significant correlation between pChk2 immunostaining intensity and percentage of pChk2 positive cells in tumors and demonstrated that high-grade serous carcinomas expressed an elevated level of pChk2 as compared to low-grade serous carcinomas. Normal ovarian, fallopian tube, ovarian cyst, and serous borderline tumors did not show detectable pChk2 immunoreactivity. There was no significant difference in pChk2 immunoreactivity between primary and recurrent high-grade serous carcinomas. In high-grade serous carcinomas, a significant correlation (P<0.0001) in expression level (both in intensity and percentage) was found between pChk2 and Rsf-1 (HBXAP), a gene involved in chromatin remodeling that is amplified in high-grade serous carcinoma. Our results suggest that the DNA damage response is common in high-grade ovarian serous carcinomas, especially those with Rsf-1 overexpression, suggesting that Rsf-1 may be associated with DNA damage response in high-grade serous carcinomas.

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Vang, Russell, Ie-Ming Shih, and Robert J. Kurman. "Ovarian Low-grade and High-grade Serous Carcinoma." Advances in Anatomic Pathology 16, no. 5 (September 2009): 267–82. http://dx.doi.org/10.1097/pap.0b013e3181b4fffa.

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Moss, Esther Louise, Tim Evans, Philippa Pearmain, Sarah Askew, Kavita Singh, Kiong K. Chan, Raji Ganesan, and Lynn Hirschowitz. "Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?" International Journal of Gynecologic Cancer 25, no. 7 (September 2015): 1201–7. http://dx.doi.org/10.1097/igc.0000000000000477.

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IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

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Voutsadakis, Ioannis A. "Low-grade serous ovarian carcinoma: an evolution toward targeted therapy." International Journal of Gynecologic Cancer 30, no. 10 (November 27, 2019): 1619–26. http://dx.doi.org/10.1136/ijgc-2019-000832.

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Low-grade serous ovarian carcinoma and its high-grade serous ovarian carcinoma counterpart differ in their precursor lesions, molecular profile, natural history, and response to therapies. As such, low-grade serous ovarian carcinoma needs to be studied separately from high-grade serous ovarian carcinoma, despite challenges stemming from its rarity. A deeper understanding of the pathogenesis of low-grade serous ovarian carcinoma and the most common molecular defects and pathways involved in the carcinogenesis of the ovarian epithelium from normal to serous borderline ovarian tumors to low-grade serous ovarian carcinoma will help develop better therapies. By adopting targeted approaches there may be an opportunity to integrate novel therapies without the need for robust numbers in clinical trials. This manuscript will discuss low-grade serous ovarian carcinoma and focus on the arising treatments being developed with an improved understanding of the pathogenesis of this disease.

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Kenda Šuster, Nataša, Snježana Frković Grazio, Irma Virant-Klun, Ivan Verdenik, and Špela Smrkolj. "Cancer Stem Cell–Related Marker NANOG Expression in Ovarian Serous Tumors: A Clinicopathological Study of 159 Cases." International Journal of Gynecologic Cancer 27, no. 9 (November 2017): 2006–13. http://dx.doi.org/10.1097/igc.0000000000001105.

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ObjectiveThe objectives of this study were to assess cancer stem cell–related marker NANOG expression in ovarian serous tumors and to evaluate its prognostic significance in relation to ovarian serous carcinoma.MethodsNANOG protein expression was immunohistochemically evaluated in the ovarian tissue microarrays of 20 patients with benign ovarian serous tumors, 30 patients with borderline ovarian serous tumors, and 109 patients with ovarian serous carcinomas, from which 106 were of high-grade and 3 of low-grade morphology Immunohistochemical reaction was scored according to signal intensity and the percentage of positive cells in tumor samples. Pursuant to our summation of signal intensity and positive cell occurrence, we divided our samples into 4 groups: NANOG-negative, NANOG–slightly positive, NANOG–moderately positive, and NANOG–strongly positive group. Complete clinical data were obtained for the ovarian serous carcinoma group, and correlation between clinical data and NANOG expression was analyzed.ResultsA specific brown nuclear, or cytoplasmic reaction, was considered a positive NANOG staining. In terms of the ovarian serous carcinoma group, 69.7% were NANOG positive, 22.9% slightly positive, 22.9% moderately positive, and 23.9% strongly positive. All NANOG-positive cases were of high-grade morphology. Benign and borderline tumors and low-grade serous carcinomas were NANOG negative. There was no significant correlation between NANOG expression and clinical parameters in terms of the ovarian serous carcinoma group.ConclusionsPositive NANOG expression is significantly associated with high-grade ovarian serous carcinoma and is absent in benign, borderline, and low-grade serous lesions. In our study, there was no correlation between NANOG expression and clinical parameters, including its use in the prognosis of ovarian serous carcinoma.

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Ricciardi, Enzo, Thaïs Baert, Beyhan Ataseven, Florian Heitz, Sonia Prader, Mareike Bommert, Stephanie Schneider, Andreas du Bois, and Philipp Harter. "Low-grade Serous Ovarian Carcinoma." Geburtshilfe und Frauenheilkunde 78, no. 10 (October 2018): 972–76. http://dx.doi.org/10.1055/a-0717-5411.

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AbstractIn the early 2000s a two-tier grading system was introduced for serous ovarian cancer. Since then, we have increasingly come to accept that low-grade serous ovarian carcinoma (LGSOC) is a separate entity with a unique mutational landscape and clinical behaviour. As less than 10% of serous carcinomas of the ovary are low-grade, they are present in only a small number of patients in clinical trials for ovarian cancer. Therefore the current treatment of LGSOC is based on smaller trials, retrospective series, and subgroup analysis of large clinical trials on ovarian cancer. Surgery plays a major role in the treatment of patients with LGSOC. In the systemic treatment of LGSOC, hormonal treatment and targeted therapies seem to play an important role.

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De Leo, Antonio, Donatella Santini, Claudio Ceccarelli, Giacomo Santandrea, Andrea Palicelli, Giorgia Acquaviva, Federico Chiarucci, et al. "What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors." Diagnostics 11, no. 4 (April 14, 2021): 697. http://dx.doi.org/10.3390/diagnostics11040697.

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Ovarian carcinomas represent a heterogeneous group of neoplasms consisting of separate entities with distinct risk factors, precursor lesions, pathogenesis, patterns of spread, molecular profiles, clinical course, response to chemotherapy, and outcomes. The histologic subtype and the related molecular features are essential for individualized clinical decision-making. The fifth edition of the World Health Organization classification of tumors of the female genital tract divides ovarian carcinomas into at least five main and distinct types of ovarian carcinomas: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, clear cell carcinoma, and mucinous carcinoma. Molecular pathology has improved the knowledge of genomic landscape of ovarian carcinomas identifying peculiar alterations for every histologic subtype. It is well-known that high-grade and low-grade serous carcinomas are separate entities with entirely different morphologic and molecular characteristics. TP53 and BRCA mutations are typical of high-grade serous carcinoma, whereas BRAF and KRAS mutations frequently occur in low-grade serous carcinoma. Endometrioid and clear cell carcinomas are frequently associated with endometriosis. Endometrioid tumors are characterized by β-catenin alterations, microsatellite instability, and PTEN and POLE mutations, while ARID1A mutations occur in both endometrioid and clear cell carcinomas. Mucinous carcinomas are uncommon tumors associated with copy-number loss of CDKN2A and KRAS alterations and metastasis from other sites should always be considered in the differential diagnosis.

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Wu, Jingjing, and Jian-Jun Wei. "HMGA2 and high-grade serous ovarian carcinoma." Journal of Molecular Medicine 91, no. 10 (May 19, 2013): 1155–65. http://dx.doi.org/10.1007/s00109-013-1055-8.

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Bajaj, Anubha. "The Flagellate Transition- Serous Carcinoma Ovary." Women's Health Science Journal 6, no. 1 (2022): 1–4. http://dx.doi.org/10.23880/whsj-16000166.

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Serous ovarian tumours are engendered from Mullerian epithelium and denominate a segment of surface epithelial-stromal ovarian tumours. Serous ovarian carcinoma is classified as low grade tumefaction comprising of benign, borderline and low grade malignant lesions and high grade neoplasms. Staging of serous carcinoma of ovary is appropriately achieved with American Joint Committee on Cancer (AJCC), International Federation of Obstetrics and Gynaecology (FIGO) and Tumour, Node, Metastasis(TNM) staging. Surgical resection is an optimal and curative mode of therapy.

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Seidman, Jeffrey D., Anna Yemelyanova, Jonathan A. Cosin, Anthony Smith, and Robert J. Kurman. "Survival Rates for International Federation of Gynecology and Obstetrics Stage III Ovarian Carcinoma by Cell Type: A Study of 262 Unselected Patients With Uniform Pathologic Review." International Journal of Gynecologic Cancer 22, no. 3 (March 2012): 367–71. http://dx.doi.org/10.1097/igc.0b013e31823c6f80.

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ObjectivePublished data are conflicting on the influence of cell type on prognosis in ovarian cancer. The recent separation of low-grade serous carcinoma as a distinctive cell type of ovarian cancer with an indolent behavior, in retrospect, suggests that survival in studies that have not separated this group may be inaccurate.MethodsAn unselected series of 262 International Federation of Gynecology and Obstetrics stage III ovarian carcinomas was studied. Diagnostic classification of each tumor was made with particular attention to recent refinements in cell-type classification. Survival curves were constructed according to Kaplan-Meier and compared with the log-rank test.ResultsThe 5-year survival for 207 high-grade serous carcinomas was 40%, as compared with 71% for 18 patients with low-grade serous carcinoma (P = 0.0113). Low-grade serous carcinoma was significantly more likely to be optimally debulked (P = 0.0039) and significantly less likely to be substage IIIC (P < 0.0001). The survival for carcinosarcoma was significantly inferior to all serous carcinomas (P = 0.0322). The significance of this latter comparison was lost when carcinosarcomas were compared with only high-grade serous carcinoma (P > 0.05).ConclusionsLow-grade serous carcinoma has a significantly better prognosis than high-grade serous carcinoma and also differs with regard to substage distribution and proportion of patients optimally debulked. Because of its excellent prognosis, failure to separate low-grade serous carcinomas, notwithstanding its infrequent occurrence, can change the results of survival analyses that do not make this separation.

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Boyd, Clinton, and W. Glenn McCluggage. "Low-Grade Ovarian Serous Neoplasms (Low-Grade Serous Carcinoma and Serous Borderline Tumor) Associated With High-Grade Serous Carcinoma or Undifferentiated Carcinoma." American Journal of Surgical Pathology 36, no. 3 (March 2012): 368–75. http://dx.doi.org/10.1097/pas.0b013e31823732a9.

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Punzón-Jiménez, Paula, Victor Lago, Santiago Domingo, Carlos Simón, and Aymara Mas. "Molecular Management of High-Grade Serous Ovarian Carcinoma." International Journal of Molecular Sciences 23, no. 22 (November 9, 2022): 13777. http://dx.doi.org/10.3390/ijms232213777.

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High-grade serous ovarian carcinoma (HGSOC) represents the most common form of epithelial ovarian carcinoma. The absence of specific symptoms leads to late-stage diagnosis, making HGSOC one of the gynecological cancers with the worst prognosis. The cellular origin of HGSOC and the role of reproductive hormones, genetic traits (such as alterations in P53 and DNA-repair mechanisms), chromosomal instability, or dysregulation of crucial signaling pathways have been considered when evaluating prognosis and response to therapy in HGSOC patients. However, the detection of HGSOC is still based on traditional methods such as carbohydrate antigen 125 (CA125) detection and ultrasound, and the combined use of these methods has yet to support significant reductions in overall mortality rates. The current paradigm for HGSOC management has moved towards early diagnosis via the non-invasive detection of molecular markers through liquid biopsies. This review presents an integrated view of the relevant cellular and molecular aspects involved in the etiopathogenesis of HGSOC and brings together studies that consider new horizons for the possible early detection of this gynecological cancer.

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Cojocaru, E., C. A. Parkinson, and J. D. Brenton. "Personalising Treatment for High-Grade Serous Ovarian Carcinoma." Clinical Oncology 30, no. 8 (August 2018): 515–24. http://dx.doi.org/10.1016/j.clon.2018.05.008.

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SANTILLAN, A., Y. W. KIM, M. L. ZAHURAK, G. J. GARDNER, R. L. GIUNTOLI, I. M. SHIH, and R. E. BRISTOW. "Differences of chemoresistance assay between invasive micropapillary/low-grade serous ovarian carcinoma and high-grade serous ovarian carcinoma." International Journal of Gynecological Cancer 17, no. 3 (May 2007): 601–6. http://dx.doi.org/10.1111/j.1525-1438.2007.00820.x.

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Gokadze, Nadezhda, Vladimir Selchuk, G. Krasnoshchekova, Yuliya Payanidi, Svetlana Vinokurova, and Kirill Zhordania. "IMMUNOCYTOCHEMICAL ANALYSIS OF ASPIRATION MATERIAL FROM THE UTERINE SEROUS OVARIAN CANCER DETECTION." Problems in oncology 66, no. 2 (February 1, 2020): 160–66. http://dx.doi.org/10.37469/0507-3758-2020-66-2-160-166.

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Objective of the study: To increase the efficiency of the diagnosis of serous ovarian cancer by the method of immunocytochemical (ICC) analysis of the expression of p53, p16, wt1 markers in cells obtained in aspiration material from the uterine cavity. Materials and methods: The cellular expression of p53, p16 and wt1 markers was determined in aspiration material from uterine cavity of 71 patients with a morphologically confirmed diagnosis of serous ovarian cancer III-IV stages (51 patients with high grade serous carcinoma and 20 patients with low grade). The results were compare with cellular expression of the same markers in groups of patients with benign ovarian tumors (n = 50), patients with secondary (metastatic) ovarian lesions (n = 50) and healthy women (n = 50). The study did not include patients with early stages of ovarian cancer because of too small number of similar cases . For cytological studies, cytopin multilayer preparations of the cytospin system were obtained. An ICC study was conducted with monoclonal antibodies to p53, p16, wt1. Results: p53 demonstrated the greatest diagnostic significance in group of patients with high grade serous carcinomas: expression was traced in 31 of 51 observations of serous carcinomas of the ovaries, which amounted to 61%. A positive reaction of wt1 was observed in 24 of 51 cases (47%), p16 expression was observed in 25 of 51 cases (49%). In the group of patients with low grade serous carcinomas (n = 20), in contrast to the group of patients with high grade serous ovarian cancer, a positive reaction of p53 was observed in 3 out of 20 cases (15%), p16 in 2 (10%), but wt1 expressed in samples of 12 (60%) patients. By ICC examination of samples collected from uterine cavity of patients with benign ovarian tumors we identify focal moderate expression of p53 in separate endometrial epithelial calls in 2 cases. Histologically, serous cystadenoma of the ovaries was detected in these patients, and in another 48 samples no positive reactions with antibodies to p53,p16,wt1 were observed. In group of patients with secondary lesion of the ovaries, as well as in the control group, positive marker reactions were not observed. Conclusions: The increased expression of p53, p16, wt1 markers in cells obtained by aspiration from the uterine cavity during an ICC study can be used as a diagnostic test for high grade serous carcinoma.

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Kohn, Elise C., and S. Percy Ivy. "Whence High-Grade Serous Ovarian Cancer." American Society of Clinical Oncology Educational Book, no. 37 (May 2017): 443–48. http://dx.doi.org/10.1200/edbk_174718.

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Our understanding of epithelial ovarian cancer has blossomed, and we now recognize that it is a collection of varied histologic and molecularly different malignancies, many of which may not derive from a true ovarian anatomic precursor. High-grade serous ovarian cancer (HGSOC) is a unique type of epithelial cancer. It is characterized by nearly universal mutation in and dysfunction of p53, genomic instability rather than driver mutations, advanced stage at onset, and probable fallopian tube epithelium origin, with a serous tubal in situ carcinoma precursor. Germline deleterious mutations in BRCA1 and BRCA2, as well as other less prevalent genes involved in DNA repair, such as PALB2 and RAD51c, are associated with its carcinogenesis and may predict susceptibility to classes of treatment agents, including DNA-damaging agents and DNA repair inhibitors. Loss of function of these genes is associated with homologous recombination dysfunction (HRD). It is now recognized that there may be HGSOC with wild-type BRCA1 and BRCA2 with an identifiable HRD phenotype. Such HRD tumors also may be more susceptible to certain classes of treatments and may be phenotypically detectable with a composite molecular biomarker that has been shown to be predictive for response to PARP inhibitors. Use of this new knowledge of the anatomic and molecular background of HGSOC has led to the rational design of novel combinations of treatment classes to create an HRD-like cellular environment and thus drive treatment benefits.

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Okoye, Ekene, Elizabeth D. Euscher, and Anais Malpica. "Ovarian Low-grade Serous Carcinoma." American Journal of Surgical Pathology 40, no. 5 (May 2016): 627–35. http://dx.doi.org/10.1097/pas.0000000000000615.

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Gross, Amy L., Robert J. Kurman, Russell Vang, Ie-Ming Shih, and Kala Visvanathan. "Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics." Journal of Oncology 2010 (2010): 1–9. http://dx.doi.org/10.1155/2010/126295.

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The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC), particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs) but our own findings (unpublished data) and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs).

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Koshiyama, Masafumi, Noriomi Matsumura, and Ikuo Konishi. "Recent Concepts of Ovarian Carcinogenesis: Type I and Type II." BioMed Research International 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/934261.

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Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may developde novofrom the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC) arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT). With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs) of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ), undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells.

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Kepuladze, Shota, Tamar Dzotsenidze, Arsen Gvenetadze, Mariam Gachechiladze, and George Burkadze. "Immunohistochemical phenotype of fallopian tubes in patients with different grades of serous ovarian carcinoma." Indian Journal of Pathology and Oncology 9, no. 4 (December 15, 2022): 301–5. http://dx.doi.org/10.18231/j.ijpo.2022.073.

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During recent years, there is an accumulating evidence that high grade ovarian carcinoma is developed from the fallopian tube epithelial lesions. However, is not yet completely understood and still represents the subject of investigation. We investigated the immunohistochemical phenotype of matched fallopian tubes from the patients with different types and malignancy grades of ovarian carcinoma. Matched fallopian tubes from ovarian cancer patients were available in 260 cases, including mucinous borderline tumor (n=25), mucinous carcinoma (n=15), serous borderline tumor (n=90), low grade serous carcinoma (n=72) and high grade serous carcinoma (n=48). Immunohistochemical investigation included markers of proliferation (Ki67), apoptosis (Bcl2, p53), hormone receptors (ER, PR), epithelial differentiation (CK7), mesenchymal differentiation (vimentin, calretinin) and stem cells (CD44). The results indicate that the presence of fallopian tube carcinoma in situ is significantly correlated with the presence of high grade ovarian serous carcinoma (r=0.44, p<0.001), whilst there was no significant association with low grade and borderline serous tumors or mucinous tumors.

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Dowson, Cassandra B., Colin Stewart, Sarah O'Sullivan, Nicholas Pachter, Lyn Schofield, and Paul A. Cohen. "Incidence of germline BRCA1/2 mutations in women with tubo-ovarian high-grade serous carcinomas with and without serous tubal intra-epithelial carcinomas." International Journal of Gynecologic Cancer 30, no. 1 (November 7, 2019): 94–99. http://dx.doi.org/10.1136/ijgc-2019-000540.

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ObjectiveTo compare the germline BRCA1 and BRCA2 mutation (gBRCA) status in women with high-grade serous tubo-ovarian and primary peritoneal carcinoma with and without serous tubal intra-epithelial carcinomas (serous tubal intra-epithelial carcinoma-positive vs serous tubal intra-epithelial carcinoma-negative).Materials and methodsA retrospective study was performed of patients in Western Australia diagnosed with high-grade serous tubo-ovarian and primary peritoneal carcinoma and referred for genetic counseling and gBRCA testing from July 1, 2014 to June 30, 2017. Histopathology reports were reviewed to ascertain whether serous tubal intra-epithelial carcinoma was present. Personal or family gBRCA status, family history, age at diagnosis, mode of treatment (neoadjuvant chemotherapy vs primary surgery), and stage were also recorded.ResultsA total of 269 women with high-grade serous tubo-ovarian and primary peritoneal carcinoma were referred for genetic counseling and testing. 114 patients were excluded because the serous tubal intra-epithelial carcinoma status was not assessable or because patients did not attend for genetic assessment. 155 patients (55 serous tubal intra-epithelial carcinoma-positive and 100 serous tubal intra-epithelial carcinoma-negative) underwent genetic testing. gBRCA mutations were found in 27.8% of serous tubal intra-epithelial carcinoma-positive patients compared with 14.0% of serous tubal intra-epithelial carcinoma-negative patients (p=0.094). Of those found to have a gBRCA mutation, 89.7% reported a positive personal or family history of BRCA-related cancers.ConclusionsThe gBRCA mutation detection rate in serous tubal intra-epithelial carcinoma-positive patients was nearly double that of serous tubal intra-epithelial carcinoma-negative patients. Factors such as a positive family history of BRCA-related cancers were seen at a higher proportion in the mutation positive women.

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Georgescu, Tiberiu-Augustin, Roxana Bohiltea, Octavian Munteanu, Corina Grigoriu, Ioana Paunica, and Maria Sajin. "A mini-review regarding the carcinogenesis and morphology of serous tumors of the ovary, fallopian tube and peritoneum." Journal of Mind and Medical Sciences 8, no. 1 (April 15, 2021): 44–52. http://dx.doi.org/10.22543/7674.81.p4452.

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Similar to the already well-recognized adenoma-carcinoma sequence in colorectal cancer pathogenesis, it has been believed for many decades that the progression of ovarian epithelial tumors occurs from benign serous cystadenomas to borderline tumors, to well-differentiated carcinomas, and ultimately, to poorly differentiated carcinomas. However, it is currently accepted that low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC) are fundamentally different tumor types and, consequently, different diseases. In fact, whereas the benign-borderline-malignant sequence seems to apply quite well to low-grade serous carcinoma, the sequence of genetic alterations in high-grade serous carcinoma is substantially different. In this mini-review, we included the current consensus regarding the morphological and etiopathogenic results regarding serous tumors of the ovary, fallopian tube and peritoneum. It also briefly describes the history of benign, borderline and malignant serous tumors, discussing multiple types of dichotomies in serous carcinomas of the female genital tract and summarizing the current molecular classification.

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Salvador, Shannon, Blake Gilks, Martin Köbel, David Huntsman, Barry Rosen, and Dianne Miller. "The Fallopian Tube: Primary Site of Most Pelvic High-grade Serous Carcinomas." International Journal of Gynecologic Cancer 19, no. 1 (2009): 58–64. http://dx.doi.org/10.1111/igc.0b013e318199009c.

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Epithelial ovarian cancer is the most common cause of mortality from gynecologic malignancy, and most of epithelial cancers are of serous type. The site of origin of pelvic high-grade serous carcinoma has been the subject of debate for 60 years. This paper reviews the evidence that pelvic serous carcinoma originates from the fallopian tube mucosa and puts forward a theory that inflammation in the tube, caused by menstrual cytokines or infection, is critical to the genesis of these tumors. Other risk factors for pelvic serous carcinoma will be reviewed, including oral contraceptive use, parity, infertility, and tubal ligation.Studies were identified for this review by searching the English language literature in the MEDLINE database between the years 1995 and 2007 using the following keywords: fallopian tube neoplasia, ovarian serous adenocarcinoma, pregnancy, oral contraceptive, infertility, pelvic inflammatory disease, cytokines, menstruation, and tubal ligation, followed by an extensive review of bibliographies from articles found through the search.The clinical implications of this theory are discussed, and a change in surgical practice is recommended, with salpingectomy at the time of simple hysterectomy. This theory also has implications for the development of new methods of screening for pelvic serous carcinomas, as there are no screening methods that are currently available to find this form of cancer in an early stage. Inflammatory markers could be detected in the vagina from the fallopian tube indicating possible chronic inflammation and a risk factor for mutagenesis leading to serous carcinoma.

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Stur, Elaine, Sara Corvigno, Mingchu Xu, Ken Chen, Yukun Tan, Sanghoon Lee, Jinsong Liu, et al. "Spatially resolved transcriptomics of high-grade serous ovarian carcinoma." iScience 25, no. 3 (March 2022): 103923. http://dx.doi.org/10.1016/j.isci.2022.103923.

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Bromley, Amy B., Alon D. Altman, Pamela Chu, Jill G. Nation, Gregg S. Nelson, Praful Ghatage, Steve E. Kalloger, Guangming Han, and Martin Köbel. "Architectural Patterns of Ovarian/Pelvic High-grade Serous Carcinoma." International Journal of Gynecological Pathology 31, no. 5 (September 2012): 397–404. http://dx.doi.org/10.1097/pgp.0b013e31824c2372.

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28

O'Neill, C. J., H. A. McBride, L. E. Connolly, M. T. Deavers, A. Malpica, and W. G. McCluggage. "High-grade ovarian serous carcinoma exhibits significantly higher p16 expression than low-grade serous carcinoma and serous borderline tumour." Histopathology 50, no. 6 (May 2007): 773–79. http://dx.doi.org/10.1111/j.1365-2559.2007.02682.x.

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29

Santandrea, Giacomo, Simonetta Piana, Riccardo Valli, Magda Zanelli, Elisa Gasparini, Antonio De Leo, Vincenzo Dario Mandato, and Andrea Palicelli. "Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature." Diagnostics 11, no. 2 (January 29, 2021): 199. http://dx.doi.org/10.3390/diagnostics11020199.

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The term “ovarian carcinoma” encompasses at least five different malignant neoplasms: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma. These five histotypes demonstrated distinctive histological, molecular, and clinical features. The rise of novel target therapies and of a tailored oncological approach has demanded an integrated multidisciplinary approach in the setting of ovarian carcinoma. The need to implement a molecular-based classification in the worldwide diagnostic and therapeutic setting of ovarian cancer demanded a search for easy-to-use and cost-effective molecular-surrogate biomarkers, relying particularly on immunohistochemical analysis. The present review focuses on the role of immunohistochemistry as a surrogate of molecular analysis in the everyday diagnostic approach to ovarian carcinomas.

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Nahar, Begum Afrin, Rama Saha, Chhanda Das, and Gourishankar Kamilya. "Immunohistochemical expression of human epididymis 4 in ovarian malignancy." International Journal of Research in Medical Sciences 7, no. 12 (November 27, 2019): 4493. http://dx.doi.org/10.18203/2320-6012.ijrms20195506.

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Background: Ovarian malignancies has the highest mortality rate among all gynaecological malignancies. Surface epithelial tumors form two thirds of all ovarian neoplasm and 90% of all ovarian cancers are surface epithelial carcinomas. Mortality in case of ovarian malignancy is high due to late diagnosis. Early and accurate diagnosis can improve the case specific management. HE4 (Human Epididymis Protein 4) which is proved to be overexpressed in the ovarian cancer cells, is considered a new biomarker for ovarian cancer diagnosis which helps in early diagnosis and patient management. Aims and objectives of the study was to evaluate the immunohistochemical expression of HE4 in various ovarian malignancies.Methods: It was a cross sectional, prospective, single institution-based study, conducted in the department of Pathology in collaboration with the Department of Gynaecology and Obstetrics, from December 2016 to January 2019 in institution. A total 74 ovarian malignancies were selected for this study.Results: Serous carcinoma was the most common ovarian malignancy followed by endometrioid carcinoma. Highest percentage of expression of HE4 was seen in high grade serous cancer and malignant endometrioid tumor.Conclusions: HE4 was highly expressed in malignant ovarian tumour especially serous and endometrioid carcinoma and can be used as an important biomarker for malignant ovarian neoplasm. Expression in high grade ovarian serous cancer support its prognostic value also.

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Manchana, Tarinee, Ruangsak Lertkhachonsuk, and Chinachote Teerapakpinyo. "Somatic BRCA Mutation in High Grade Epithelial Ovarian Cancer Patients." Asian Pacific Journal of Cancer Biology 3, no. 4 (January 9, 2019): 99–103. http://dx.doi.org/10.31557/apjcb.2018.3.4.99-103.

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Aim: To identify the frequency of somatic BRCA mutation in epithelial ovarian cancer (EOC), particularly those with high grade subtypes. Methods: Patients diagnosed with EOC included fallopian tube cancer or peritoneal cancer who had surgery during January 2015 to December 2016 were included. High grade subtypes included high grade serous carcinoma, poorly differentiated endometrioid carcinoma, and clear cell carcinoma. BRCA1 and BRCA2 mutations were tested using DNA extracted from formalin-fixed paraffin embedded block or a fresh tumor specimen then analyzed by next generation sequencing system. Patients who had no germline BRCA mutation in their peripheral blood DNA investigated by bi-directional Sanger sequencing were diagnosed as having somatic BRCA mutation.Results: 36 patients were enrolled; majority of the patients (33patients; 97.2%) had EOC, 1 patient (2.8%) had fallopian tube cancer and 2 patients (5.6%) had peritoneal cancer. 28 patients (77.8%) had high grade serous carcinoma, 6 (16.7%) had poorly differentiated endometrioid carcinoma, and 2 (5.6%) had clear cell carcinoma. BRCA1 mutation was detected in tumor tissues of 2 patients (5.6%). These two patients had high grade serous carcinoma and significant family history of breast and/or ovarian cancers. However, BRCA1 mutations were detected in the peripheral blood in both of them.Conclusion: Only 5.6% of BRCA1 mutation was detected in ovarian tumor tissues, all mutations were found in high grade serous subtype. However, BRCA mutations were detected in the peripheral blood in both of them. Germline BRCA mutation was diagnosed, thus there were no somatic mutations in this study.

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Levanon, Keren, Christopher Crum, and Ronny Drapkin. "New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact." Journal of Clinical Oncology 26, no. 32 (November 10, 2008): 5284–93. http://dx.doi.org/10.1200/jco.2008.18.1107.

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There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.

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Kim, Jaeyeon, Eun Park, Olga Kim, Jeanne Schilder, Donna Coffey, Chi-Heum Cho, and Robert Bast. "Cell Origins of High-Grade Serous Ovarian Cancer." Cancers 10, no. 11 (November 12, 2018): 433. http://dx.doi.org/10.3390/cancers10110433.

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High-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), is the most common and deadliest type of ovarian cancer. HGSC appears to arise from the ovary, fallopian tube, or peritoneum. As most HGSC cases present with widespread peritoneal metastases, it is often not clear where HGSC truly originates. Traditionally, the ovarian surface epithelium (OSE) was long believed to be the origin of HGSC. Since the late 1990s, the fallopian tube epithelium has emerged as a potential primary origin of HGSC. Particularly, serous tubal intraepithelial carcinoma (STIC), a noninvasive tumor lesion formed preferentially in the distal fallopian tube epithelium, was proposed as a precursor for HGSC. It was hypothesized that STIC lesions would progress, over time, to malignant and metastatic HGSC, arising from the fallopian tube or after implanting on the ovary or peritoneum. Many clinical studies and several mouse models support the fallopian tube STIC origin of HGSC. Current evidence indicates that STIC may serve as a precursor for HGSC in high-risk women carrying germline BRCA1 or 2 mutations. Yet not all STIC lesions appear to progress to clinical HGSCs, nor would all HGSCs arise from STIC lesions, even in high-risk women. Moreover, the clinical importance of STIC remains less clear in women in the general population, in which 85–90% of all HGSCs arise. Recently, increasing attention has been brought to the possibility that many potential precursor or premalignant lesions, though composed of microscopically—and genetically—cancerous cells, do not advance to malignant tumors or lethal malignancies. Hence, rigorous causal evidence would be crucial to establish that STIC is a bona fide premalignant lesion for metastatic HGSC. While not all STICs may transform into malignant tumors, these lesions are clearly associated with increased risk for HGSC. Identification of the molecular characteristics of STICs that predict their malignant potential and clinical behavior would bolster the clinical importance of STIC. Also, as STIC lesions alone cannot account for all HGSCs, other potential cellular origins of HGSC need to be investigated. The fallopian tube stroma in mice, for instance, has been shown to be capable of giving rise to metastatic HGSC, which faithfully recapitulates the clinical behavior and molecular aspect of human HGSC. Elucidating the precise cell(s) of origin of HGSC will be critical for improving the early detection and prevention of ovarian cancer, ultimately reducing ovarian cancer mortality.

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Khatun, Dr Most Fatema, Dr Md Zahangir Alam, Dr Md Bani Amin, Dr Milan Kumar Saha, Dr Shamima Hamid, and Dr Md Samsuzzaman Khan. "Study on P53 Expression in Association with Histopathological Grading of Ovarian Serous Carcinoma." Scholars Journal of Applied Medical Sciences 9, no. 10 (October 24, 2021): 1584–90. http://dx.doi.org/10.36347/sjams.2021.v09i10.019.

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Background: Ovarian cancer is a disease of significant morbidity and mortality. It is the most common cancer among women worldwide. Early and accurate detection and grading of ovarian serous carcinoma is of utmost significance for prolongation of patient survival. Panels of immunomarkers have been tested to overcome limitation of histopathology. Immunomarker p53 is commonly used among them. This study was undertaken to evaluate the significance of p53 immunomarker in ovarian serous carcinoma. Objective: Objective of this study to see p53 expression and its association with different histopathological grading of ovarian serous carcinoma. Method: This cross-sectional study was conducted in the Department of Pathology, Rajshahi Medical College, over a period of two years from July 2017 to June 2019. A total of 32 clinically suspected cases of ovarian carcinoma admitted in the RMCH and later on histologically confirmed as ovarian serous carcinoma were included in the study. Histories of the patient were obtained from the hospital records. Tissue biopsy from the site of lesion or operated specimen of tissue was fixed with 10% formalin and was processed stained with haematoxyline and eosin stain and was examined. Result: Immunohistochemistry was done for p53 from significant paraffin embedded block. Of the 32 cases 20 were histologically confirmed as high grade and the rest 12 were low grade ovarian serous carcinoma. In this present study, age distribution showed that, about 60% of the patients were within 2nd to 5thdecades.The mean age of the patients was 41.34 years. The sensitivity of p53 was found high (80.2%) in case of serous ovarian carcinoma and its different grade. Conclusion: The study concluded that p53 is a highly sensitive immunomarker for detecting the grade of ovarian carcinoma specially serous ovarian carcinoma.

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Ulianova, E. P., E. M. Nepomnyashchaya, G. V. Zhukova, A. B. Sagakyants, D. Yu Yakubova, and O. G. Shulgina. "ABC transporters in the development of platinum drug resistance in serous ovarian carcinoma." CLINICAL AND EXPERIMENTAL MORPHOLOGY 11, no. 2 (2022): 13–21. http://dx.doi.org/10.31088/cem2022.11.2.13-21.

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Introduction. Serous ovarian carcinoma is a group of extremely aggressive malignant tumors with high mortality rates; today, it remains the most prognostically unfavorable gynecologic cancer in the world. One of the causes is the development of multidrug resistance after administration of various chemotherapy regimens. Therefore, the search for effective markers of resistance to chemotherapy in this disease is promising. The purpose of this study was to analyze expressions of ABC transporters Pgp (ABCB1) and BCRP (ABCG2) in cells of high-grade serous ovarian carcinomas in patients with varying sensitivity to platinum-based polychemotherapy. Materials and methods. Tumor tissues of 100 patients aged 29–79 years with high-grade serous ovarian carcinomas and stages IIIC–IV were studied with immunohistochemical method with rabbit P-glycoprotein 1 (Pgp or MDR1) polyclonal antibodies and by the Reveal Polyvalent HRP-DAB Detection System with mouse monoclonal BCRP antibodies (JF0994 clone). We used the Statistica 13.0 program (StatSoftInc., USA) to analyze the results. We determined the Mann–Whitney U and Pearson’s χ² values, as well as odds ratios with CI. Results. In groups with platinum resistance and platinum sensitivity, there prevailed patients with Pgp+ (98% and 68%) and BCRP+ (90% and 81.4%). Mann–Whitney U-test showed that in cancer cells in platinum-resistant patients, the expression of Pgp and BCRP (70;40–100 and 65;45–90) was 1.8 (p=0.003) and 1.9 times (p=0.013) higher, respectively, than in platinum-sensitive patients (40;4–65 and 35;10–60). Conclusion. The results on the Pgp marker show that it can be used as a predictive factor in high-grade serous ovarian carcinomas. Keywords: serous ovarian carcinoma, multidrug resistance, ABC transporters, Pgp, BCRP

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SALANI, R., R. J. KURMAN, R. GIUNTOLI, G. GARDNER, R. BRISTOW, T. L. WANG, and I. M. SHIH. "Assessment of TP53 mutation using purified tissue samples of ovarian serous carcinomas reveals a higher mutation rate than previously reported and does not correlate with drug resistance." International Journal of Gynecologic Cancer 18, no. 3 (May 2008): 487–91. http://dx.doi.org/10.1111/j.1525-1438.2007.01039.x.

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The TP53 mutation frequency in ovarian serous carcinomas has been reported to range between 50% and 80%, but a stringent analysis of TP53 using purified epithelial samples has not yet been performed to accurately assess the mutation frequency and to correlate it with the histologic grade. The purpose of this study was to assess the TP53 mutational profile in a relatively large series of high-grade (53 primary and 18 recurrent) and 13 low-grade ovarian serous tumors using DNA isolated from affinity-purified tumor cells and to correlate it with in vitro drug resistance. All samples were affinity purified, and the tumor DNA was analyzed for TP53 mutations in exons 4–9. In vitro drug resistance assays to carboplatin, cisplatin, paclitaxel, and taxotere were performed on the same tumor samples and correlated with the TP53 mutation status. TP53 mutations were detected in 57 (80.3%) of 71 high-grade carcinomas and in one (7.8%) of 13 low-grade serous tumors (an invasive low-grade serous carcinoma). The mutations were predominantly missense mutations (59.6%). TP53 mutations were associated with high-grade serous carcinomas and recurrent disease (P < 0.0001). There was no statistically significant correlation between TP53 mutation status and drug resistance assays or clinical stage (P > 0.25). The frequency of TP53 mutations using purified tumor DNA from ovarian serous carcinomas was 80.3%, which is much higher than previously reported. Furthermore, we found that TP53 is not directly involved in the development of drug resistance in high-grade ovarian serous carcinomas.

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Estrella, Jeannelyn S., Judith K. Wolf, and Michael T. Deavers. "Ovarian Serous Carcinoma Associated With a Distinct “Corded and Hyalinized” Pattern." Archives of Pathology & Laboratory Medicine 137, no. 2 (February 1, 2013): 275–79. http://dx.doi.org/10.5858/arpa.2011-0200-cr.

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The “corded and hyalinized” pattern, described in endometrioid carcinoma, has not been previously reported in association with serous carcinoma. We describe a unique case of serous neoplasm of low malignant potential with low-grade serous carcinoma combined with a distinct pattern of high-grade carcinoma characterized by cords of epithelioid and spindled cells enmeshed in a hyalinized, collagenous stroma. This pattern was the predominant architecture in the patient's recurrence and caused a diagnostic challenge, as the splenic recurrence was initially diagnosed as a second primary high-grade spindle cell neoplasm. Both ovarian and splenic tumors displayed positive immunohistochemical staining for cytokeratin 7, cytokeratin 8/18, estrogen receptor, and paired box gene 8 (PAX-8) in the conventional serous carcinoma and the corded and hyalinized component, confirming the diagnosis of recurrent carcinoma. The behavior in this unique case of serous carcinoma associated with a distinct corded and hyalinized pattern was more aggressive than low-grade serous carcinoma, but more favorable than malignant mixed mullerian tumor.

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Morency, Elizabeth, Mario M. Leitao, and Robert A. Soslow. "Low-Stage High-Grade Serous Ovarian Carcinomas." International Journal of Gynecological Pathology 35, no. 3 (May 2016): 222–29. http://dx.doi.org/10.1097/pgp.0000000000000256.

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Osman Mohamed, Aisha, Nazik Elmalaika Husain, Rawia Eljaili Elmassry, Lubna Alnageeb, Mohammed Elhassan, and Mohammed Siddig Abdelaziz. "Immunohistochemical expression of p53 in Type I and II epithelial ovarian cancer among Sudanese women: a cross-sectional study." F1000Research 8 (October 10, 2019): 1739. http://dx.doi.org/10.12688/f1000research.20608.1.

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Background: Epithelial ovarian cancer (EOC) represents the leading cause of death from gynecologic malignancies worldwide. In Sudan, ovarian cancer represents the fourth most frequent tumors among females. TP53 somatic mutations is a defining feature of ovarian high-grade serous carcinoma. However, p53 sequencing is not feasible in most low- and middle-income countries, like Sudan, and its frequency varies greatly. The study aimed to determine the frequency of p53 overexpression and its relationship with tumor types I and II and tumor grade among Sudanese women with EOC. Methods: In this cross-sectional, hospital-based study a total of 114 paraffin-embedded tissue blocks previously diagnosed as epithelial ovarian cancer were collected from six governmental hospitals in Khartoum state, Sudan, in the period 2013-2016. Immunohistochemistry was performed on tissue microarray slides to measure the protein expression of p53 in the EOC. Results: Overexpression of p53 was detected in 35.1% (n=40/114) of EOC samples, with a higher frequency in women with Type II 53.7% (n= 29/54) than type I 18.5% (n= 10/54) (P= 0.000). Also, a high frequency of p53 overexpression was evident in 49.2% (n= 30/61) of high-grade carcinoma compared with 16.7% (n= 1/6) of non-graded borderline tumors, and in 19.1% (n= 9/47) of low-grade tumors (P= 0.003). A high-grade serous carcinoma harbor p53 overexpression in 53.7% (n= 29/54) and none of low-grade serous carcinoma harbor p53 overexpression. Our result showed a significant association between p53 overexpression and tumor types and grades (P = 0.000 and 0.003, respectively) Conclusion: p53 over-expression was detected in one-third of Sudanese women with EOC. It was more common in type II EOC and high-grade serous, but negative in low-grade serous tumors. Our result showed a significant association between p53 over-expression and tumor type and grade, and can help discriminate between high- and low-grade serous carcinomas.

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Paris, Elizabeth A., Janice M. Bahr, Sanjib Basu, and Animesh Barua. "Changes in Nucleolin Expression during Malignant Transformation Leading to Ovarian High-Grade Serous Carcinoma." Cancers 15, no. 3 (January 21, 2023): 661. http://dx.doi.org/10.3390/cancers15030661.

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Objective: Ovarian high-grade serous carcinoma (HGSC) is a fatal malignancy of women. Alterations in the expression of nuclear proteins are early steps in malignant transformation; nucleolin is one such protein. Changes in nucleolin expression and circulatory levels during ovarian HGSC development are unknown. The study goal was to determine if tissue and circulatory levels of nucleolin change in response to malignant transformation leading to ovarian HGSC. Methods: Sera, ovaries, and BRCA+ fimbria from healthy subjects, and sera and tumor tissues from patients (n = 10 each), and healthy hens and hens with HGSC were examined in exploratory and prospective studies for nucleolin expression by immunohistochemistry, immunoblotting, gene expression, and immunoassay, and analyzed by analysis of variance (ANOVA). Results: Compared with normal, nucleolin expression was higher in patients and hens with ovarian HGSC and in women with a risk of HGSC (P < 0.05). Compared with normal (1400 + 105 pg/mL, n = 8), serum nucleolin levels were 1.5 and 1.7-fold higher in patients with early- (n = 5) and late-stage (n = 5) HGSC, respectively. Additionally, serum nucleolin levels increased significantly (P < 0.05) prior to the formation of detectable masses. Conclusion: This pilot study concluded that tissue and serum levels of nucleolin increase in association with malignant changes in ovaries and fimbriae leading to ovarian HGSC.

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Cho, Kathleen R. "Ovarian Cancer Update: Lessons From Morphology, Molecules, and Mice." Archives of Pathology & Laboratory Medicine 133, no. 11 (November 1, 2009): 1775–81. http://dx.doi.org/10.5858/133.11.1775.

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Abstract Ovarian carcinomas are a heterogeneous group of neoplasms. Pathologists currently employ a morphology-based classification system to divide ovarian carcinomas into major subgroups based on degree (tumor grade) and type of differentiation (eg, serous, endometrioid, clear cell, or mucinous). Molecular studies have shown that specific genetic defects are likely to be present in certain histologic types of ovarian carcinomas and unlikely to be present in others. Within the serous and endometrioid carcinomas, the molecular defects in low-grade versus high-grade tumors also appear to be largely distinct. Recently, mouse models of ovarian carcinoma have been developed that recapitulate many of the morphologic features and biologic behavior of selected subtypes of ovarian cancer. It is expected that these mouse models will yield new insights into ovarian cancer pathogenesis and prove useful for preclinical testing of novel strategies for ovarian cancer treatment.

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Zhang, Li, Po Ding, Hongcheng Lv, Dan Zhang, Guang Liu, Zhengduo Yang, Yan Li, Jun Liu, and Shiwu Zhang. "Number of Polyploid Giant Cancer Cells and Expression of EZH2 Are Associated with VM Formation and Tumor Grade in Human Ovarian Tumor." BioMed Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/903542.

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Анотація:

To investigate the associations among the number of polyploid giant cancer cells (PGCCs) and vasculogenic mimicry (VM), EZH2 expression, and serous ovarian tumor grade, a total of 80 paraffin-embedded serous ovarian tumor samples including 21 cases of primary carcinoma and their metastatic tumors, 26 cases of primary carcinoma without metastasis, and 12 cases of serous borderline cystadenoma were analyzed. PGCCs and VM were detected in human serous ovarian tumor. The metastatic foci of ovarian carcinoma had the highest number of PGCCs and VM. The number of PGCCs and VM increased with the grade of ovarian carcinomas. PGCCs generated erythrocytes via budding and together they formed VM. Tumor cells and cancer-associated fibroblasts were positive for EZH2 immunohistochemical staining. The tumor cells and cancer associated fibroblasts in the metastatic foci had the highest staining index of EZH2 staining. Both tumor cells and cancer-associated fibroblasts express EZH2 which then contributes to the malignant grade of serous ovarian tumor.

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Dergham, Ana Paula, Caroline Busatta Vaz de Paula, Seigo Nagashima, Márcia Olandoski, Lucia de Noronha, and Vanessa Santos Sotomaior. "Immunohistochemical Profiling of PD-1, PD-L1, CD8, MSI, and p53 and Prognostic Implications in Advanced Serous Ovarian Carcinoma: A Retrospective Study." Journal of Personalized Medicine 13, no. 7 (June 26, 2023): 1045. http://dx.doi.org/10.3390/jpm13071045.

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Анотація:

Advanced high-grade serous ovarian carcinoma is a serious malignant neoplasm with a late diagnosis and high mortality rate. Even when treated with standard therapy, such as surgery followed by carboplatin and paclitaxel chemotherapy, the prognosis remains unfavorable. Immunotherapy is a treatment alternative that requires further study. Therefore, we aimed to evaluate the expression of PD-1, PD-L1, CD8, MSI (MLH1, MSH2, MSH6, and PMS2), and p53 in the paraffin samples of high-grade serous ovarian carcinoma. A retrospective study of 28 southern Brazilian patients with advanced serous ovarian carcinoma (EC III or IV) was conducted between 2009 and 2020. The expression of these proteins was evaluated using immunohistochemistry, and the results were correlated with the patients’ clinicopathological data. At diagnosis, the mean age was 61 years, and the most common clinical stage (60%) was EC III. Among the cases, 84.6% exhibited p53 overexpression, 14.8% had MSI, 92.0% were sensitive to platinum, and more than 50.0% relapsed after treatment. Patients with MSI had a lower CD8/PD-1 ratio and more relapses (p = 0.03). In conclusion, analysis of immunotherapeutic markers in paraffin-embedded advanced serous ovarian carcinoma samples is feasible and may assist in prognosis.

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Kutlvasr, K., K. Bukovjan, and R. Kodet. "Bilateral low grade serous adenocarcinoma of the ovaries in a badger (Meles meles L.) and its association with a borderline serous ovarian tumour: a case report." Veterinární Medicína 59, No. 1 (February 14, 2014): 44–50. http://dx.doi.org/10.17221/7245-vetmed.

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Here, we describe a case of a wild female badger (a sow) with disseminated serous adenocarcinoma of the ovary which corresponds to a group of low grade serous carcinomas of the ovary in humans. Beside grossly apparent dissemination of the disease we observed a scale of histological features classifiable as a precursor lesion – borderline serous tumour of the ovary with implant metastases at the peritoneum, and features of the borderline tumour transformation in the carcinoma. The latter features included invasion of some of the metastatic peritoneal implants into the adipose tissue of the mesentery, retroperitoneum, and in the muscle of diaphragm with lymphangioinvasion and with blood-borne metastatic disease in the lungs. The primary tumour and its metastases had a uniform cytological appearance without atypia of the tumour cells. Mitotic activity was exceptional. The proliferation activity as demonstrated by immunohistochemical investigation of Ki-67 protein expression (revealing all active phases of the cell cycle – G1, S, G2, M) showed a low proliferation activity of the tumour cells, comparable with findings in low grade carcinomas or borderline tumours of the ovaries in women. WT1 protein was expressed in the whole tumour cell population. All these features were diagnostic of serous carcinoma of the ovary with low grade malignant potential. Tumours of the ovaries in wildlife have been described previously but they are infrequent and are rarely classified histopathologically. This case report offers a parallel with serous carcinomas in human pathology including features of transformation from a precursor lesion of a borderline serous tumour into a serous low grade carcinoma.  

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Khashaba, Marwa, Reham Nagib, azza abdelaziz, Ghada Eladawy, and Mohammed Mohamed. "Clinicopathological and Immunohistochemical Study of High Grade Serous Ovarian Carcinoma." Medicine Updates 2, no. 2 (July 1, 2020): 15–37. http://dx.doi.org/10.21608/muj.2020.29356.1011.

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Kurman, R. J. "Origin and molecular pathogenesis of ovarian high-grade serous carcinoma." Annals of Oncology 24 (December 2013): x16—x21. http://dx.doi.org/10.1093/annonc/mdt463.

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Chen, Gregory M., Lavanya Kannan, Ludwig Geistlinger, Victor Kofia, Zhaleh Safikhani, Deena M. A. Gendoo, Giovanni Parmigiani, Michael Birrer, Benjamin Haibe-Kains, and Levi Waldron. "Consensus on Molecular Subtypes of High-Grade Serous Ovarian Carcinoma." Clinical Cancer Research 24, no. 20 (July 3, 2018): 5037–47. http://dx.doi.org/10.1158/1078-0432.ccr-18-0784.

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Singh, Naveena, W. Glenn McCluggage, and C. Blake Gilks. "High-grade serous carcinoma of tubo-ovarian origin: recent developments." Histopathology 71, no. 3 (July 18, 2017): 339–56. http://dx.doi.org/10.1111/his.13248.

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49

Messini, Irini, Triada Doulgeraki, Dimitris Chrysanthakis, Petros Yiannou, Theofani Gavresea, Christos Papadimitriou, Theodoros Panoskaltsis, Zannis Voulgaris, Athanassios Vlachos, and Kitty Pavlakis. "Assessing the landscape of ovarian serous borderline tumors." International Journal of Gynecologic Cancer 29, no. 3 (January 18, 2019): 572–78. http://dx.doi.org/10.1136/ijgc-2018-000086.

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AimTo compare distinct clinicopathological features between atypical proliferative serous tumors and non-invasive low-grade ovarian serous carcinomas.MethodsOur study group comprised 203 cases of serous borderline tumors sub-classified as atypical proliferative serous tumors or as non-invasive low-grade serous carcinomas. All pathological features related to borderline tumors were re-evaluated by two gynecological pathologists. Data concerning recurrences and survival were retrieved from the medical records of the patients.ResultsWhen comparing atypical proliferative serous tumors to non-invasive low-grade serous carcinomas, the latter were statistically related to advanced stage at diagnosis, bilateral disease, exophytic pattern of growth, microinvasive carcinoma, and the presence of invasive implants. In univariate analysis, recurrences were statistically related to the exophytic pattern of growth, to microinvasion, and to the presence of implants (both invasive and non-invasive). Nevertheless, in multivariate analysis, only microinvasion and the presence of invasive implants were related to recurrence. Women who eventually succumbed to the disease were only those with invasive implants. Their ovarian tumor was either a non-invasive low-grade serous carcinoma or an atypical proliferative serous tumor with ‘minimal’ micropapillary pattern. Neither lymph node involvement nor endosalpingiosis seemed to influence the course of the disease.ConclusionsThe results of our study underline the increased possibility of non-invasive low-grade serous carcinomas to be related with features indicative of aggressive behavior as opposed to atypical proliferative serous tumors. Nevertheless, irrespective of tumor histology, the presence of invasive implants and microinvasion were the only independent prognostications of recurrence.

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Gilks, C. Blake. "Molecular Abnormalities in Ovarian Cancer Subtypes Other than High-Grade Serous Carcinoma." Journal of Oncology 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/740968.

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Ovarian cancer is the fifth leading cause of cancer death in women in North America, and approximately two-thirds of cases of ovarian cancer are of high-grade serous type. The remaining cases are comprised of a mix of different tumor types (e.g., endometrioid, clear cell, mucinous, etc.), with no single tumor type accounting for more than 10% of ovarian cancer cases. These tumor types can be reproducibly diagnosed, and each features distinct underlying molecular events during oncogenesis, with a characteristic natural history and response rate to conventional cytotoxic chemotherapy. In this review the molecular abnormalities present in the more common non-high-grade serous subtypes of ovarian cancer will be presented. Development of targeted therapies for these tumor types will require understanding of the genetic basis of each tumor type, and may lead to subtype-specific therapy.

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