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Gasparis, Przyborowski, Kała, and Nadolska-Orczyk. "Knockout of the HvCKX1 or HvCKX3 Gene in Barley (Hordeum vulgare L.) by RNA-Guided Cas9 Nuclease Affects the Regulation of Cytokinin Metabolism and Root Morphology." Cells 8, no. 8 (July 26, 2019): 782. http://dx.doi.org/10.3390/cells8080782.
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Barley is among four of the most important cereal crops with respect to global production. Increasing barley yields to desired levels can be achieved by the genetic manipulation of cytokinin content. Cytokinins are plant hormones that regulate many developmental processes and have a strong influence on grain yield. Cytokinin homeostasis is regulated by members of several multigene families. CKX genes encode the cytokinin oxidase/dehydrogenase enzyme, which catalyzes the irreversible degradation of cytokinin. Several recent studies have demonstrated that the RNAi-based silencing of CKX genes leads to increased grain yields in some crop species. To assess the possibility of increasing the grain yield of barley by knocking out CKX genes, we used an RNA-guided Cas9 system to generate ckx1 and ckx3 mutant lines with knockout mutations in the HvCKX1 and HvCKX3 genes, respectively. Homozygous, transgene-free mutant lines were subsequently selected and analyzed. A significant decrease in CKX enzyme activity was observed in the spikes of the ckx1 lines, while in the ckx3 lines, the activity remained at a similar level to that in the control plants. Despite these differences, no changes in grain yield were observed in either mutant line. In turn, differences in CKX activity in the roots between the ckx1 and ckx3 mutants were reflected via root morphology. The decreased CKX activity in the ckx1 lines corresponded to greater root length, increased surface area, and greater numbers of root hairs, while the increased CKX activity in the ckx3 mutants gave the opposite results. RNA-seq analysis of the spike and root transcriptomes revealed an altered regulation of genes controlling cytokinin metabolism and signaling, as well as other genes that are important during seed development, such as those that encode nutrient transporters. The observed changes suggest that the knockout of a single CKX gene in barley may be not sufficient for disrupting cytokinin homeostasis or increasing grain yields.
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Köllmer, Ireen, Ondřej Novák, Miroslav Strnad, Thomas Schmülling, and Tomáš Werner. "Overexpression of the cytosolic cytokinin oxidase/dehydrogenase (CKX7) from Arabidopsis causes specific changes in root growth and xylem differentiation." Plant Journal 78, no. 3 (April 7, 2014): 359–71. http://dx.doi.org/10.1111/tpj.12477.
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Schwarz, Ireen, Marie-Therese Scheirlinck, Elisabeth Otto, Isabel Bartrina, Ralf-Christian Schmidt, and Thomas Schmülling. "Cytokinin regulates the activity of the inflorescence meristem and components of seed yield in oilseed rape." Journal of Experimental Botany 71, no. 22 (September 10, 2020): 7146–59. http://dx.doi.org/10.1093/jxb/eraa419.
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Abstract The number of flowers and seed-bearing structures formed by the inflorescence meristem and the formation of ovules in the female reproductive part of the flowers are important yield-related traits of crop plants. It has been shown that cytokinin is a pivotal factor regulating these traits. Here, we explore the impact of mutation of CYTOKININ OXIDASE/DEHYDROGENASE (CKX) genes encoding cytokinin-degrading enzymes on these yield-related traits in oilseed rape (Brassica napus L.). We describe the identification of four BnCKX3 and two BnCKX5 genes as regulators of reproductive development in the allotetraploid B. napus. RNA-seq analysis and in situ hybridization showed expression of these genes in reproductive organs. Loss-of-function mutants for each of these CKX gene copies were identified by targeting induced local lesions in genomes (TILLING) and combined by crossing. Sextuple ckx3 ckx5 mutants showed an increased cytokinin concentration and larger and more active inflorescence meristems. They also produced up to 72% more flowers with gynoecia containing 32% more ovules and up to 54% more pods on the main stem. The weight of seeds harvested from the main stem of plants grown in the greenhouse or in the field was increased by 20–32%. Our results show that cytokinin regulates inflorescence meristem and placenta activity in oilseed rape. The work demonstrates the potential to achieve yield enhancement in a dicot crop plant by modulating the cytokinin status through mutagenesis of specific CKX genes.
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Niemann, Michael C. E., Isabel Bartrina, Angel Ashikov, Henriette Weber, Ondřej Novák, Lukáš Spíchal, Miroslav Strnad, et al. "Arabidopsis ROCK1 transports UDP-GlcNAc/UDP-GalNAc and regulates ER protein quality control and cytokinin activity." Proceedings of the National Academy of Sciences 112, no. 1 (December 22, 2014): 291–96. http://dx.doi.org/10.1073/pnas.1419050112.
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The formation of glycoconjugates depends on nucleotide sugars, which serve as donor substrates for glycosyltransferases in the lumen of Golgi vesicles and the endoplasmic reticulum (ER). Import of nucleotide sugars from the cytosol is an important prerequisite for these reactions and is mediated by nucleotide sugar transporters. Here, we report the identification of REPRESSOR OF CYTOKININ DEFICIENCY 1 (ROCK1, At5g65000) as an ER-localized facilitator of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) transport in Arabidopsis thaliana. Mutant alleles of ROCK1 suppress phenotypes inferred by a reduced concentration of the plant hormone cytokinin. This suppression is caused by the loss of activity of cytokinin-degrading enzymes, cytokinin oxidases/dehydrogenases (CKXs). Cytokinin plays an essential role in regulating shoot apical meristem (SAM) activity and shoot architecture. We show that rock1 enhances SAM activity and organ formation rate, demonstrating an important role of ROCK1 in regulating the cytokinin signal in the meristematic cells through modulating activity of CKX proteins. Intriguingly, genetic and molecular analysis indicated that N-glycosylation of CKX1 was not affected by the lack of ROCK1-mediated supply of UDP-GlcNAc. In contrast, we show that CKX1 stability is regulated in a proteasome-dependent manner and that ROCK1 regulates the CKX1 level. The increased unfolded protein response in rock1 plants and suppression of phenotypes caused by the defective brassinosteroid receptor bri1-9 strongly suggest that the ROCK1 activity is an important part of the ER quality control system, which determines the fate of aberrant proteins in the secretory pathway.
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Carrasco, Cristian, Andrés Tittarelli, Natalia Paillaleve, Maeva Del Pozo, Daniel Rojas-Sepúlveda, Omar Barría, Paula Fluxá, et al. "The Evaluation of 17 Gastrointestinal Tumor Markers Reveals Prognosis Value for MUC6, CK17, and CD10 in Gallbladder-Cancer Patients." Diagnostics 11, no. 2 (January 21, 2021): 153. http://dx.doi.org/10.3390/diagnostics11020153.
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Gallbladder cancer (GBC) is an aggressive and highly lethal disease with relatively low global incidence, but one that constitutes a major health problem in Asian and Latin American countries, particularly in Chile. The identification of new tumor-associated markers with potential prognosis value is required for GBC clinical practice. Using immunohistochemistry/tumor tissue microarray, we evaluated the expression of 17 gastrointestinal tumor-associated protein markers (CK7, CK17, CK19, CK20, CKLMW, CKHMW, MUC1, MUC2, MUC5AC, MUC6, CA125, CD10, CEA, vimentin, villin, claudin-4, and CDX2) in primary gallbladder adenocarcinomas from 180 Chilean patients and analyzed potential associations with their pathological and clinical characteristics. Younger female patients with well- to moderately differentiated tumors had a better prognosis than that of older female or male patients with tumors with a similar tumor differentiation grade. Among all analyzed markers, MUC6 expression was associated with better prognosis in patients with well- to moderately differentiated tumors, whereas CK17 or CD10 was associated with worse prognosis in patients with poorly differentiated tumors. In addition, the MUC6+CK17– expression pattern was strongly associated with better prognosis in patients with well- to moderately differentiated tumors, whereas patients with poorly differentiated tumors and with the CK17+CD10+ expression pattern showed worse prognosis. Our results suggest that tumor MUC6, CK17, and CD10 can be considered as potential prognosis markers for GBC.
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Mühlhauser, J., C. Crescimanno, M. Kasper, D. Zaccheo, and M. Castellucci. "Differentiation of human trophoblast populations involves alterations in cytokeratin patterns." Journal of Histochemistry & Cytochemistry 43, no. 6 (June 1995): 579–89. http://dx.doi.org/10.1177/43.6.7539466.
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Cytokeratins (CKs) are related to proliferation and differentiation of epithelial cells. Little knowledge exists about CK patterns in human trophoblast subpopulations (villous and extravillous trophoblasts). To better understand differentiation and function of trophoblast components, we studied the distribution patterns of CKs in the placenta throughout pregnancy. A panel of well-defined monoclonal antibodies against different types of cytokeratins, vimentin, and fibrin, was used on frozen and paraffin sections. CK8, 18, and 19 were expressed in all the villous and extravillous trophoblastic subsets throughout pregnancy. In the first trimester, syncytiotrophoblasts were positive for CK7 and 13 along the basal membrane. As pregnancy progressed there was an increase in intensity of the reaction product and a more diffuse positive staining of CK7 in the cytoplasm of the syncytium, with evident positivity along the apical membrane. CK13 showed similar expression as CK7, but with less intense staining along the apical membrane and less prominent staining in the cytoplasm. Villous cytotrophoblasts were also positive for CK7 and CK13. CK17 was found related to cytotrophoblastic cells in contact with or next to fibrin deposits. Extravillous cytotrophoblasts in cell islands and cell columns were positive for CK13 only in the cell layers located proximal to the villous stroma, whereas the distal and more differentiated cells were negative. CK7 was positive in all epithelial cells of cell islands and columns, but the reaction product was not present in cells deeply migrated into the decidua. Amnion was negative for anti-CK13 antibodies in the first trimester but was positive at term. CK4 and CK16 were not found in the placenta. Our study shows for the first time that the different populations of human placental trophoblast express cytokeratins in developmental, differentiative, and functional specific patterns. These findings can be useful to distinguish and classify the various trophoblastic populations and provide a foundation for studying pathological aspects of the trophoblast.
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Liu, Yang, Xun Wang, Xiaofei Wang, Wensheng Gao, and Chunxiang You. "Identification and Functional Characterization of Apple MdCKX5.2 in Root Development and Abiotic Stress Tolerance." Horticulturae 8, no. 1 (January 10, 2022): 62. http://dx.doi.org/10.3390/horticulturae8010062.
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Cytokinin oxidase/dehydrogenases (CKXs) are the key enzymes in cytokinin degradation and have been widely studied in model plants. Little is known about apple’s (Malus×domestica) CKX genes. Here, using genome-wide analysis, we identified 10 MdCKX genes in apple. The phylogenetics, chromosome locations, and genome structures were then tested. Expression analysis showed that MdCKX genes had different expression profiles in apple, pointing to the different roles. Meanwhile, relative expression analysis showed that these genes have different expression patterns in response to several exogenous cytokinin factors, including trans-zeatin (ZT), thidiazuron (TDZ), and N6-furfuryladenine (KT). Finally, we introduced the MdCKX5.2 gene into Arabidopsis to evaluate its functions, and the results suggested the transgenic Arabidopsis displayed phenotypes related to promoting primary root and lateral root development, response to exogenous ZT, and conferring to drought and salt tolerant. Taken together, our results provide insights on the possible application of the MdCKX5.2 gene for molecular breeding in apples.
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Sanguansin, Sirima, Theerachai Kosanwat, Rachai Juengsomjit, and Sopee Poomsawat. "Diagnostic Value of Cytokeratin 17 during Oral Carcinogenesis: An Immunohistochemical Study." International Journal of Dentistry 2021 (November 22, 2021): 1–9. http://dx.doi.org/10.1155/2021/4089549.
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Background. Little is known about the role of cytokeratin 17 (CK17) during oral carcinogenesis. CK17 expression in oral leukoplakia (OL), the most encountered oral potentially malignant disorders and oral squamous cell carcinoma (OSCC), remains very limited. To determine the role of CK17 during oral carcinogenesis and its potential diagnostic marker in oral premalignant and malignant lesions, this study evaluated CK17 expression in OL without dysplasia, OL with dysplasia, and OSCC. CK17 expression in these tissues was compared with those of normal oral mucosa (NOM). Additionally, the relationship between CK17 expression and clinicopathologic factors of OSCC was investigated. Methods. CK17 expression was evaluated in 186 samples consisting of 12 NOM, 33 OL without dysplasia, 58 OL with dysplasia, and 83 OSCC using immunohistochemistry. The proportion of positively immunostained cells was evaluated and scored. Results. CK17 was expressed in 8.3%, 54.5%, 74.1%, and 90.4% of NOM, OL without dysplasia, OL with dysplasia, and OSCC, respectively. NOM had a significantly lower CK17 score than OL with dysplasia ( p = 0.0003 ) and OSCC ( p < 0.0001 ). A significant association between CK17 expression and histopathologic differentiation of OSCC was found. Tumors with well differentiation had high CK17 expression compared with those of moderate and poor differentiation. Conclusion. CK17 was overexpressed in OL with dysplasia and OSCC, suggesting that CK17 plays a pivotal role in the development of premalignant lesions and OSCC. Of clinical significance, CK17 may be a good diagnostic marker for oral premalignant lesions and OSCC. Additionally, CK17 could be used as an objective tool to classify histopathologic grade in OSCC. The findings that CK17 expression is high in OSCC but low in NOM imply that CK17 may serve as a potential therapeutic target for OSCC.
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Liu, Haiyan, Jianhui Shi, Vasuki Anandan, Hanlin L. Wang, David Diehl, Joseph Blansfield, Glenn Gerhard, and Fan Lin. "Reevaluation and Identification of the Best Immunohistochemical Panel (pVHL, Maspin, S100P, IMP-3) for Ductal Adenocarcinoma of the Pancreas." Archives of Pathology & Laboratory Medicine 136, no. 6 (June 1, 2012): 601–9. http://dx.doi.org/10.5858/arpa.2011-0326-oa.
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Context.—Differentiation of ductal adenocarcinoma of the pancreas from nonneoplastic pancreatic tissues can be challenging, especially in small biopsy and fine-needle aspiration specimens. Objective.—To investigate the utility of 26 immunohistochemical markers (CAM 5.2, CK [cytokeratin] 7, CK20, CK17, CK19, MUC1, MUC2, MUC4, MUC5AC, MUC6, p53, DPC4/SMAD4, CDX2, pVHL [von Hippel-Lindau tumor suppressor gene protein], S100P, IMP-3 [insulin-like growth factor 2 messenger RNA binding protein 3], maspin, mesothelin, claudin 4, claudin 18, annexin A8, fascin, PSCA [prostate stem cell antigen], MOC31, CEA [carcinoembryonic antigen], and CA19-9 [cancer antigen 19-9]) in the diagnosis of ductal adenocarcinoma of the pancreas. Design.—Immunohistochemical staining for these markers was performed in 60 cases of pancreatic ductal adenocarcinoma on routine and tissue microarray sections. In addition, immunohistochemical staining for maspin, S100P, IMP-3, and pVHL was performed on cell blocks from 67 pancreatic fine-needle aspiration cases, including 44 cases of pancreatic ductal adenocarcinoma. Results.—The results demonstrated that (1) more than 90% of cases of ductal adenocarcinoma were positive for maspin, S100P, and IMP-3; (2) nearly all adenocarcinoma cases were negative for pVHL, whereas nonneoplastic ducts and acini were positive for pVHL in all cases; (3) normal/reactive pancreatic ducts were frequently positive for CK7, CK19, MUC1, MUC6, CA19-9, MOC31, PSCA, mesothelin, annexin A8, claudin 4, and claudin 18; (4) normal pancreatic ducts were usually negative for IMP-3, maspin, S100P, CK17, MUC2, MUC4, and MUC5AC; (5) 60% of adenocarcinomas were negative for DPC4/SMAD4; and (6) strong background staining was frequently seen with fascin, PSCA, and annexin A8. Conclusions.—pVHL, maspin, S100P, and IMP-3 constitute the best diagnostic panel of immunomarkers for confirming the diagnosis of pancreatic ductal adenocarcinoma in both surgical and fine-needle aspiration specimens.
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Hong, Soon Auck, Su Hyun Yoo, Jene Choi, Stanley J. Robboy, and Kyu-Rae Kim. "A Review and Update on Papillary Immature Metaplasia of the Uterine Cervix: A Distinct Subset of Low-Grade Squamous Intraepithelial Lesion, Proposing a Possible Cell of Origin." Archives of Pathology & Laboratory Medicine 142, no. 8 (April 13, 2018): 973–81. http://dx.doi.org/10.5858/arpa.2017-0267-oa.
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Context.— Papillary immature metaplasia (PIM) is a known papillary cervical lesion associated with low-risk human papillomavirus (LR-HPV). Objective.— To evaluate additional clinicopathologic features and the HPV genotypes of PIM and discuss the presumptive cell of origin. Design.— A total of 26 PIM cases were evaluated by p16INK4a, cytokeratin (CK) 7, and CK17 immunohistochemical stainings. Human papillomavirus genotyping was performed, by using HPV DNA Chip, HPV polymerase chain reaction (PCR), and real-time PCR. Results.— Histologically, PIM forms either a papillary mass (n = 21 of 26, 81%) or a slightly elevated/flat plaque (n = 5, 19%). All cases contain variable amounts of mucinous epithelia within the lesions. Koilocytosis was identified in 15 of the 26 cases (58%). Sixteen cases (61%) were associated with LR-HPV (types 6, 11, or 42), but 3 cases (12%) with high-risk (HR) HPV (16, 16/18, and 33), 2 cases (8%) with mixed LR- and HR-HPV (6/16 and 11/58), while 2 cases (8%) were negative, but p16INK4a immunostaining showed nonblock positivity in all cases. Eight (31%) had high-grade squamous intraepithelial lesion (HSIL) in the adjacent mucosa, 4 (50%) of which showed direct continuity. Identical HPV subtypes were confirmed in separately microdissected cases from PIM and adjacent HSIL. Most lesions (n = 24, 92%) expressed CK17 (reserve cell marker) in a bottom-heavy pattern and CK7 (squamocolumnar junction [SCJ] marker) in a top-heavy pattern, while most cases of low-grade squamous intraepithelial lesion (LSIL) were negative for both markers. Conclusions.— Our results suggest that PIM is a distinct subset of LSIL showing a productive HPV infection, but PIM involves the transformation zone and is proximal to SCJ, while LSIL is mostly from ectocervix or distal to the SCJ.
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Knösel, Thomas, Valeska Emde, Karsten Schlüns, Peter Michael Schlag, Manfred Dietel, and Iver Petersen. "Cytokeratin Profiles Identify Diagnostic Signatures in Colorectal Cancer Using Multiplex Analysis of Tissue Microarrays." Analytical Cellular Pathology 28, no. 4 (January 1, 2006): 167–75. http://dx.doi.org/10.1155/2006/354295.
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Background and aims: Recent cDNA expression profiling analyses indicate that within specific organ cancers Cytokeratins (CKs) dysregulation may identify subgroups with distinct biological phenotypes. Our objectives in this study were (1) to test whether cytokeratins were also distinct on the protein level, (2) to evaluate these biomarkers in a series of well-characterised CRCs, (3) to apply hierarchical cluster analysis to immunohistochemical data. Methods: Tissue microarrays (TMA) comprising 468 CRC specimens from 203 patients were constructed to evaluate CK5, CK7, CK8, CK13, CK14, CK16, CK17, CK18, CK19 and CK20. In total, 2919 samples were analyzed. Results: Unsupervised hierarchical clustering discovered subgroups represented by reduced CK8 and CK20 expression, that differed by a shorter patients survival. The evaluation of the specific biomarkers by Kaplan–Meier analysis showed that reduced CK8 expression (p < 0.01) was significantly associated with shorter patients’ survival, but was not an independent factor correlated with tumour stage (pT), grading (G) and nodal stage (pN). Conclusions: Reduced coexpression of CK8 and CK20 may indicate an epithelial-mesenchymal transition (EMT) representing an important step in the development of more aggressive CRCs. In addition, multiplex analysis of TMAs together with immunohistochemistry (IHC) supplemented by hierarchical clustering are a useful, promising and very powerful tool for the identification of tumour subgroups with diagnostic and prognostic signatures.
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Xin, Wei, Mark A. Rubin, and Paul E. McKeever. "Differential Expression of Cytokeratins 8 and 20 Distinguishes Craniopharyngioma From Rathke Cleft Cyst." Archives of Pathology & Laboratory Medicine 126, no. 10 (October 1, 2002): 1174–78. http://dx.doi.org/10.5858/2002-126-1174-deocad.
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Abstract Background.—Craniopharyngiomas are epithelial neoplasms usually located in the sellar and suprasellar regions. Distinguishing craniopharyngioma from Rathke cleft cyst is sometimes difficult, and the distinction is clinically significant because Rathke cleft cysts have a better prognosis than craniopharyngiomas. Design.—We retrieved 10 cases with a primary diagnosis of craniopharyngioma and 5 cases with a diagnosis of Rathke cleft cyst for analysis. Five cases of normal pars intermedia of pituitary glands from autopsy served as controls. We evaluated the expression patterns of a broad range of low– to intermediate–molecular weight cytokeratins (CK7, CK8, CK10, CK17, CK18, CK19, and CK20) and high–molecular weight cytokeratins (K903: a combination of CK1, CK5, CK10, and CK14; and CK5/6) in these cases. Results.—Craniopharyngiomas had a cytokeratin expression pattern distinct from that of Rathke cleft cysts and pituitary gland pars intermedia: craniopharyngiomas did not express cytokeratins 8 and 20, whereas Rathke cleft cysts and pars intermedia of pituitary glands both expressed cytokeratins 8 and 20. Conclusion.—The differential expression of cytokeratins distinguishes between craniopharyngioma and Rathke cleft cyst, and this difference could be useful for identifying craniopharyngioma in difficult cases in which only a small biopsy is available. The different cytokeratin profiles of craniopharyngioma and Rathke cleft cyst suggest that these lesions do not come from the same origin, or that they come from a different developmental stage of the pouch epithelium.
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Zhou, Jun, Xiaoqun Yang, Luting Zhou, Peipei Zhang, and Chaofu Wang. "Combined Immunohistochemistry for the “Three 7” Markers (CK7, CD117, and Claudin-7) Is Useful in the Diagnosis of Chromophobe Renal Cell Carcinoma and for the Exclusion of Mimics: Diagnostic Experience from a Single Institution." Disease Markers 2019 (October 13, 2019): 1–9. http://dx.doi.org/10.1155/2019/4708154.
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Background. There is a morphological overlap among renal epithelial tumors, particularly chromophobe renal cell carcinoma (CHRCC), clear cell renal cell carcinoma (CCRCC), renal oncocytoma (RO), and papillary renal cell carcinoma (PRCC). Discriminating between these tumors is important but sometimes challenging. This study is aimed at evaluating the clinical usefulness of the combined immunochemistry for the “three 7” markers (CK7, CD117, and Claudin-7) to distinguish chromophobe renal cell carcinoma from these mimics. Methods. Immunochemical staining for CK7, CD117, and Claudin-7 was performed in 68 CHRCCs, 199 CCRCCs, 32 ROs, and 30 PRCCs. Fluorescence in situ hybridization (FISH) was performed in some cases to exclude CCRCC and PRCC. The sensitivity (SE) and specificity (SP) for CHRCC as well as the immunoreactivity of each marker and their combinations were statistically evaluated. Results. High positive rates for CK7 (94%), CD117 (87%), Claudin-7 (94%), and their combinations (CK7+CD117, 79%; CK7+Claudin-7, 88%; CD117+Claudin-7, 82%; CK7+CD117+Claudin-7, 76%) were observed in CHRCC compared to those in CCRCC, RO, and PRCC, with increasingly higher SP when combinations of the “three 7” markers were applied (CK7, 0.80; CD117, 0.82; Claudin-7, 0.78; CK7+CD117, 0.95; CK7+Claudin-7, 0.97; CD117+Claudin-7, 0.97; CK7+CD117+Claudin-7, 1). Conclusion. CK7, CD117, and Claudin-7 are frequently expressed in CHRCC with high specificity. We recommend the routine use of these 3 markers as a routine panel when making a differential diagnosis of CHRCC and excluding other mimics.
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Dasgupta, Shatavisha, Senada Koljenović, Thierry P. P. van den Bosch, Sigrid M. A. Swagemakers, Nick M. A. van der Hoeven, Ronald van Marion, Peter J. van der Spek, Helena C. van Doorn, Folkert J. van Kemenade, and Patricia C. Ewing-Graham. "Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)." Pharmaceuticals 14, no. 4 (April 2, 2021): 324. http://dx.doi.org/10.3390/ph14040324.
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Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC—the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN (n = 56), de-VIL (n = 8), and non-dysplastic vulvar tissues (n = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN (n = 8) and de-VIL (n = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues (p < 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, TP53 mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.
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Linskey, Katy R., Devon C. Gimbel, Lawrence R. Zukerberg, Lyn M. Duncan, Peter M. Sadow, and Rosalynn M. Nazarian. "BerEp4, Cytokeratin 14, and Cytokeratin 17 Immunohistochemical Staining Aid in Differentiation of Basaloid Squamous Cell Carcinoma From Basal Cell Carcinoma With Squamous Metaplasia." Archives of Pathology & Laboratory Medicine 137, no. 11 (November 1, 2013): 1591–98. http://dx.doi.org/10.5858/arpa.2012-0424-oa.
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Context.—Basaloid squamous cell carcinoma (bSCC) is an uncommon variant of squamous cell carcinoma, which may overlap histologically with basal cell carcinoma with squamous metaplasia (BCCm). Objective.—To aid in the differentiation of these neoplasms using immunohistochemical staining because of the worse prognosis associated with bSCC. Design.—Using immunohistochemical techniques, we investigated BerEp4, cytokeratin 17 (CK17), and cytokeratin 14 (CK14) protein expression in 25 cases of bSCC (8 cutaneous [32%], 12 aerodigestive tract [48%], and 5 lymph node metastases [20%]) and 43 cases of BCCm (39 cutaneous [91%], and 4 metastases [9%]). An immunoreactivity score was assigned using the percentage of tumor cells staining and the pattern of expression. Interobserver agreement for 2 independent pathologists was assessed using a κ coefficient. Results.—The mean percentage of staining was significantly higher in BCCm, compared with bSCC (BerEp4, P = .006; CK17, P < .001; CK14, P < .001; unpaired t test), with 58% of BCCm cases (25 of 43) displaying diffuse staining for all markers, and nearly all (98%; 42 of 43) displaying diffuse staining for CK17 and CK14. In contrast, no bSCC cases (0%) displayed diffuse staining for all 3 markers, and only 8% (2 of 25) displayed diffuse staining for CK17 and CK14. High interobserver agreement was determined. Conclusions.—BerEp4 alone is unreliable for differentiation between BCCm and bSCC, and the addition of either CK14 or CK17 will augment the sensitivity and negative predictive value of BerEp4 staining in BCCm and bSCC diagnosis.
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Boricic, Novica, Ivan Boricic, Ivan Soldatovic, Jovica Milovanovic, Aleksandar Trivic, and Tatjana Terzic. "Utility of CK8, CK10, CK13, and CK17 in Differential Diagnostics of Benign Lesions, Laryngeal Dysplasia, and Laryngeal Squamous Cell Carcinoma." Diagnostics 12, no. 12 (December 16, 2022): 3203. http://dx.doi.org/10.3390/diagnostics12123203.
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There are no reliable immunohistochemical markers for diagnosing laryngeal squamous cell carcinoma (SCC) or diagnosing and grading laryngeal dysplasia. We aimed to evaluate the diagnostic utility of CK8, CK10, CK13, and CK17 in benign laryngeal lesions, laryngeal dysplasia, and laryngeal SCC. This retrospective study included 151 patients diagnosed with laryngeal papilloma, laryngeal polyps, laryngeal dysplasia, and laryngeal SCC who underwent surgical treatment between 2010 and 2020. Immunohistochemistry (IHC) was carried out using specific monoclonal antibodies against CK8, CK10, CK13, and CK17. Two experienced pathologists performed semi-quantitative scoring of IHC positivity. The diagnostic significance of the markers was analyzed. CK13 showed a sensitivity of 100% and a specificity of 82.5% for distinguishing between laryngeal SCC and laryngeal dysplasia and benign lesions. CK17 showed a sensitivity of 78.3% and specificity of 57.1% for the detection of laryngeal SCC vs. laryngeal dysplasia. CK10 showed a sensitivity of 80.0% for discriminating between low-grade and high-grade dysplasia, and a specificity of 61.1%. Loss of CK13 expression is a reliable diagnostic tool for diagnosing laryngeal lesions with malignant potential and determining resection lines. In lesions with diminished CK13 expression, CK17 could be used as an auxiliary immunohistochemical marker in diagnosing laryngeal SCC. In CK13-negative and CK17-positive lesions, CK10 positivity could be used to determine low-grade dysplasia. CK8 is not a useful IHC marker in differentiating between benign laryngeal lesions, laryngeal dysplasia, and laryngeal SCC.
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Stern, Adam W., Amanda J. Young, and Jason B. Pieper. "CYTOKERATIN PROFILES OF CANINE ANAL SAC AND HEPATOID GLAND NEOPLASMS." Taiwan Veterinary Journal 44, no. 03 (August 30, 2018): 119–23. http://dx.doi.org/10.1142/s1682648518500014.
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Ten adenocarcinomas of the apocrine gland of the anal sac and 11 hepatoid gland neoplasms were studied to determine the coordinate expression of cytokeratin 7 (CK7) and cytokeratin 14 (CK14) using commercially available antibodies. Hepatoid gland neoplasms included hepatoid gland adenomas, carcinomas and a single epithelioma. All 10 (100%) adenocarcinomas of the apocrine gland of the anal sac had CK7[Formula: see text]/CK14[Formula: see text] immunophenotype, whereas all 11 (100%) of hepatoid neoplasms expressed CK7[Formula: see text]/CK14[Formula: see text] immunophenotype. Hepatoid gland adenomas, carcinomas, and epithelioma could not be differentiated based on the cytokeratin immunophenotype. Hepatoid gland neoplasms could be differentiated from adenocarcinomas of the apocrine gland of the anal sac by differences in the CK7/CK14 immunophenotypes with a [Formula: see text]-[Formula: see text]. The results of this study provide further support for the use of coordinate expression of CK7/CK14 to differentiate apocrine gland adenocarcinomas of the anal sac (CK7[Formula: see text]/CK14[Formula: see text]) from hepatoid gland neoplasms (CK7[Formula: see text]/CK14[Formula: see text]).
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Misra, Sunayana, Kaushik Majumdar, Puja Sakhuja, Priyanka Jain, Lavleen Singh, Praveen Kumar, and AP Dubey. "Differentiating Biliary Atresia From Idiopathic Neonatal Hepatitis: A Novel Keratin 7 Based Mathematical Approach on Liver Biopsies." Pediatric and Developmental Pathology 24, no. 2 (January 13, 2021): 103–15. http://dx.doi.org/10.1177/1093526620983730.
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Background and Aims Differentiating biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is vital in routine pediatric practice. However, on liver biopsy, few cases offer a diagnostic challenge to discriminate these entities with certainty. Bile ductular reaction (DR), intermediate hepatobiliary cells (IHBC) and extra-portal ductules (EPD) indicate progenitor cell activation, as a response to various hepatic insults. The present study aims to quantify DR, IHBC and EPD by Keratin 7 (CK7) immunohistochemistry (IHC) in BA and INH and to devise a mathematical approach to better differentiate the two, especially in histologically equivocal cases. Methods A total of 98 cases were categorized on biopsy as BA, INH or equivocal histology, favoring BA or INH. CK7 DR mean, IHBC mean and EPD mean values were compared between BA and INH. A formula was derived to help distinguish these two entities, the cut-off value, sensitivity and specificity of which were determined by receiver operating characteristic (ROC) curve. This formula was applied and validated on histologically equivocal cases. Results Univariate logistic regression revealed significant difference between BA and INH with respect to CK7 DR and CK7 EPD mean (p < 0.001 in both); however, CK7 IHBC mean was not significant (p = 0.08). On multivariate logistic regression, only CK7 DR had significant impact on diagnosis (p < 0.001). A formula: (CK7 DR) 2 + (CK7 EPD)/(CK7 IHBC) was derived to help distinguish BA from INH. Cut off value of 10.5 and above, determined by ROC curve, favored a diagnosis of BA (sensitivity= 93.4%, specificity= 94.6%). Histologically equivocal and discrepant cases could be correctly categorized using this formula. Conclusions Formula using CK7 IHC parameters may aid pathologists better distinguish BA from INH, especially in histologically equivocal cases.
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Youssef, M., S. Canete-Portillo, A. Yemelyanova, and B. Ronnett. "Patterns of Cytokeratin 7 Expression in Cervical Squamous Intraepithelial Lesions." American Journal of Clinical Pathology 154, Supplement_1 (October 2020): S37. http://dx.doi.org/10.1093/ajcp/aqaa161.077.
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Abstract Introduction/Objective It has been suggested that cervical high-grade squamous intraepithelial lesions (HSIL/CIN2-3) arise from squamocolumnar junction cells that express cytokeratin 7 (CK7). Significant CK7 expression (gradation or full-thickness) has been proposed as a marker of progression of low-grade squamous intraepithelial lesions (LSIL/CIN1) to HSIL and of persistence of HSIL/CIN2. The goal of the study is to survey patterns of CK 7 expression in the different grades of squamous intraepithelial lesions (SILs). Methods 65 cervical specimens (biopsies and excisions) containing 95 lesions of different grades were assessed by immunohistochemical analysis (IHC) for CK7 expression. 26 cases contained more one lesion grade. The diagnosis of HSIL (CIN2-3) was confirmed by p16 IHC. CK7 expression was scored negative, patchy, gradation (i.e., top-down), or full-thickness pattern. In cases with heterogeneous staining, the strongest pattern was used for analysis. Results There was significant variation in patterns within morphologically contiguous lesional foci; staining heterogeneity was noted in 42% of cases. All patterns of expression were encountered in all lesion grades. LSIL/CIN1 (n=47), either alone (n=27) or in combination with HSIL (n=20), often lacked CK7 expression (53%) or were patchy (17%). The frequency of significant (gradation or full-thickness) CK7 expression in LSIL with concomitant HSIL was greater than LSIL occurring alone (40% vs. 22%, respectively). HSIL/CIN3 (n=19) was dominated by full-thickness expression (57%). HSIL/CIN2 (n=29) had a very heterogeneous spectrum of expression with 34% of cases lacking expression. Conclusion CK7 expression is variable across all grades of SILs. LSIL with concomitant HSIL was associated with significant CK7 expression more frequently than LSIL alone. Significant proportion of HSIL, particularly CIN2, lacks CK7 expression. Given this variability, caution is advised regarding the use of CK7 expression as a marker of progression.
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Ilieva, Nevena, Desislava Tashkova, Dmitrii Staykov, Denitsa Serteva, Yana Feodorova, Nikolay Mehterov, Angelina Mollova, and Svitlana Bachurska. "Immunohistochemical expression of CK20, CK7, and CDX2 in colorectal carcinoma in correlation with pathomorphological characteristics." Folia Medica 64, no. 2 (April 30, 2022): 214–20. http://dx.doi.org/10.3897/folmed.64.e60950.
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Introduction: Colorectal carcinoma is the third most common cancer worldwide. The usual immunophenotype of colorectal adenocarcinoma is CDX2 positive, CK20 positive, and CK7 negative. Aberrant expression is reported in a variety of colorectal carcinomas but its relation to morphological variables and survival data is still unclear. Aim: The aim of this study was to investigate the correlation between the aberrant immunostaining of colorectal carcinoma and different clinicopathological characteristics. Materials and methods: Immunohistochemical expression of CK20, CK7, and CDX2 was evaluated in 71 cases of colorectal carcinoma. Statistical analysis was performed to identify correlations between the morphological characteristics and the immunoprofile of colorectal carcinoma. Results: Positive cytoplasmic and/or membranous signal for CK20 was observed in 66.2% of colorectal carcinomas. CK7 positive immunostaining was seen in 7% of the cases. In terms of combined expression of CK20 and CK7, the proportion of immunoprofile CK20+/CK7− was the highest, accounting for 46 out of 71 colorectal carcinomas, followed by CK20−/CK7−, then CK20−/CK7+ and CK20+/CK7+. Concerning CDX2, the majority of colorectal carcinomas (87.3%) showed positive staining. Statistically significant correlation was established between CDX2 expression and histologic grade and depth of tumour invasion. Loss of CK20 positivity was associated with higher histologic grade. No association between CK7 expression and histopathologic features was established. Conclusions: The results support the heterogeneity of colorectal cancer. Over 35% of the cases in this study showed deviations from the expected immunoprofile. This should be taken into consideration when diagnosing colorectal carcinoma in metastatic regions.
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Duval, Jennie V., Louis Savas, and Barbara F. Banner. "Expression of Cytokeratins 7 and 20 in Carcinomas of the Extrahepatic Biliary Tract, Pancreas, and Gallbladder." Archives of Pathology & Laboratory Medicine 124, no. 8 (August 1, 2000): 1196–200. http://dx.doi.org/10.5858/2000-124-1196-eocaic.
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Abstract Background.—Expression of cytokeratins 7 (CK7) and 20 (CK20) may help distinguish the site of origin for metastatic carcinomas. Little is known regarding their expression in biliary tract and pancreatic carcinomas. Our aim was to study the expression of CK7 and CK20 in these tumors. Design.—Fifty-three carcinomas of the extrahepatic bile ducts (n = 8), ampulla of Vater (n = 7), gallbladder (n = 11), and pancreas (n = 27), were retrieved from the surgical pathology files of the University of Massachusetts Medical Center. Formalin-fixed, paraffin-embedded sections were immunostained with mouse monoclonal antibodies to CK7 and CK20 using an avidin-biotin immunoperoxidase technique with microwave antigen retrieval. The percentage of cells positive for each antibody was assessed on a scale of 0 to 3 (0, <10%; 1+, 10% to 50%; 2+, 51% to 90%; 3+, >90%). Results.—The majority of carcinomas in all groups were positive for CK7 (CK7+) and negative for CK20 (CK20−). Of the CK7+ tumors, the majority of tumors in each group were 3+ positive. Conclusions.—(1) Carcinomas of the extrahepatic biliary tract and pancreas are strongly positive for CK7 and negative for CK20 and can be included in the differential diagnosis of other carcinomas with this profile in metastatic sites. (2) The CK7/CK20 immunostaining profile will not identify the site of origin for tumors with extensive growth in the porta hepatis region.
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Ernst, Linda M., Nancy B. Spinner, David A. Piccoli, Joanne Mauger, and Pierre Russo. "Interlobular Bile Duct Loss in Pediatric Cholestatic Disease is Associated with Aberrant Cytokeratin 7 Expression by Hepatocytes." Pediatric and Developmental Pathology 10, no. 5 (September 2007): 383–90. http://dx.doi.org/10.2350/06-09-0171.1.
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The objective of this study was to determine whether aberrant hepatic expression of cytokeratin 7 (CK7) and/or other putative stem cell markers is seen in pediatric cholestatic diseases. Eighteen liver biopsies and 14 liver explants from pediatric patients with extrahepatic biliary atresia (EHBA), Alagille syndrome (AGS), primary sclerosing cholangitis (PSC), inborn errors of bile acid synthesis, and progressive familial intrahepatic cholestasis (PFIC) were examined along with 5 histologically normal control liver biopsies. Immumohistochemical stains (CK7, CD56, and OV6) were performed on paraffin-embedded tissue. Staining of interlobular bile ducts (ILBD), proliferating bile ductules, and hepatocytes was scored using a semiquantitative scale. There were significant differences in CK7 staining of hepatocytes among the cholestatic diseases ( P < 0.006). All cases with AGS showed CK7 hepatocyte staining, while EHBA and PSC had variable hepatocyte staining. Patients with PFIC had prominent CK7 hepatocyte staining, while those with inborn errors of bile acid synthesis had little. Control biopsies showed rare hepatocyte staining. Analysis based on the presence or absence of ILBD revealed significantly more CK7 hepatocyte staining in cases with loss of ILBD ( P < 0.001). CD56 staining of hepatocytes was also present more frequently in cases with absent or reduced ILBD. Regardless of underlying disease, loss of ILBD is a major determinant of aberrant expression of CK7 by hepatocytes. Aberrant CK7 expression may reflect a metaplastic change to a “stem cell” phenotype induced by loss of contact with the more distal biliary tree.
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Killana, Santhosh Rupa, Prasad Uma, Atla Bhagya Lakshmi, Uttapalla Laxmi Trivedi, Juthuga Hari Chandan Kumar, and Gera Arjuna. "Clinicohistopathological study and expression of CK7 and CK20 in mucinous tumors of gastrointestinal tract and ovary." International Journal of Research in Medical Sciences 10, no. 2 (January 29, 2022): 488. http://dx.doi.org/10.18203/2320-6012.ijrms20220297.
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Background: Mucinous ovarian tumors differ from other types of epithelial ovarian cancers in their clinical behaviour and the need for innovative treatment approaches to achieve improved patient outcomes. Immunohistochemistry plays an important role in diagnosis and differentiates primary and secondary mucinous tumors. To know the distribution and expression of CK7 and CK20 in mucinous tumors of ovary and gastrointestinal tract.Methods: Ninety eight cases of mucinous tumors of ovary and gastrointestinal tract were analysed as per standard protocol out of which malignant mucinous tumors constituted forty five cases. All 45 cases of mucinous carcinoma of ovary and gastrointestinal tract were subjected to IHC CK7 and CK20. The results were analysed.Results: Total mucinous tumors of ovary were 64 cases and total mucinous tumors of gastrointestinal tract were 34 cases. Predominant expression in primary mucinous carcinoma of ovary was CK7 positive and CK20 positive, in metastatic mucinous ovarian carcinoma of gastric origin was CK7 positive and CK20 positive and from colorectal origin was CK7 negative and CK20 positive. Signet ring cell carcinoma of stomach showed CK7 diffuse positivity with focal CK20 positivity. Colorectal mucinous carcinoma was CK7 negative and CK20 positive. The expression varied with the stage of the disease.Conclusions: CK7 and CK20 plays an important role in differentiating primary mucinous carcinoma of ovary from metastatic ovarian carcinoma arising from lower gastrointestinal tract.CK7 and CK 20 expression is variable with stage of disease hence should be interpreted in the background of histopathology.
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Matsukuma, Karen E., and Elizabeth A. Montgomery. "Tubular carcinoids of the appendix: the CK7/CK20 immunophenotype can be a diagnostic pitfall." Journal of Clinical Pathology 65, no. 7 (March 29, 2012): 666–68. http://dx.doi.org/10.1136/jclinpath-2011-200639.
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AimsTubular carcinoid is a rare variant of appendiceal well-differentiated neuroendocrine tumour. Although considered benign lesions, the small infiltrating tubules that characterise the tumour may raise concern for metastatic adenocarcinoma. To our knowledge, the cytokeratin 7 (CK7)/cytokeratin 20 (CK20) expression profile of these neoplasms remains unexplored.MethodsThe authors characterised the CK7/CK20 immunophenotype and Ki-67 expression of the eight available tubular carcinoids seen at their institution from 1991 to 2011.ResultsCK7 and CK20 staining was variable, ranging from none to focal staining for either or both CK7 and CK20, to diffuse expression of CK7 or CK20.ConclusionsThe CK7/CK20 expression profile is of limited value when the differential diagnosis includes primary tubular carcinoid and well-differentiated metastatic adenocarcinoma. In such cases, careful attention to the location of the neoplasm, mitotic count and presence or absence of an associated classic carcinoid component are more useful for arriving at the correct diagnosis.
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Vaseva, I., D. Todorova, J. Malbeck, A. Travničkova, and I. Machačkova. "Mild temperature stress modulates cytokinin content and cytokinin oxidase/dehydrogenase activity in young pea plants." Acta Agronomica Hungarica 57, no. 1 (March 1, 2009): 33–40. http://dx.doi.org/10.1556/aagr.57.2009.1.4.
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Cytokinin oxidase/dehydrogenase (CKX: EC 1.5.99.12) is able to provide a means for the rapid turnover of its substrate and it has been considered responsible for changes in the cytokinin pool in an adverse environment. Mild temperature stresses (10°C and 33°C average) were applied to young pea plants of two varieties (cvs. Manuela and Scinado) in order to assess the response of the cytokinin pool and CKX activity to altered growth conditions. Both temperature treatments increased the isopentenyl adenine (iP) and isopentenyl adenine riboside (iPR) contents in stressed plants. This trend was far more pronounced in the leaves. Low temperature additionally resulted in elevated cis zeatin riboside ( cis ZR) and CKX activity. Heat did not influence the enzymatic activity in the leaves, while opposing trends were observed in the root-derived CKX activity of the two tested varieties. The data suggest that variance in the temperature provokes adaptive reactions in the cytokinin pool, which is maintained by CKX activity.
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Ma, Juanjuan, Lingling Xie, Qian Zhao, Yiting Sun, and Dong Zhang. "Cyclanilide Induces Lateral Bud Outgrowth by Modulating Cytokinin Biosynthesis and Signalling Pathways in Apple Identified via Transcriptome Analysis." International Journal of Molecular Sciences 23, no. 2 (January 6, 2022): 581. http://dx.doi.org/10.3390/ijms23020581.
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Cyclanilide (CYC), a plant growth regulator, is a potent shoot branching agent in apple. However, its mechanism remains unclear. The current study revealed that CYC treatment resulted in massive reprogramming of the axillary bud transcriptome, implicating several hormones in the response. We observed a marked increase (approximately 2-fold) in the level of zeatin riboside and a significant decrease (approximately 2-fold) in the level of abscisic acid (ABA). Zeatin metabolism gene cytokinin (CTK) oxidase 1 (CKX 1) was down-regulated at 168 h after CYC treatment compared with the control. Weighted gene co-expression network analysis of differentially expressed genes demonstrated the turquoise module clusters exhibited the highest positive correlation with zeatin riboside (r = 0.92) and the highest negative correlation with ABA (r = −0.8). A total of 37 genes were significantly enriched in the plant hormone signal transduction pathway in the turquoise module. Among them, the expressions of CTK receptor genes WOODEN LEG and the CTK type-A response regulators genes ARR3 and ARR9 were up-regulated. ABA signal response genes protein phosphatase 2C genes ABI2 and ABI5 were down-regulated in lateral buds after CYC treatment at 168 h. In addition, exogenous application of 6-benzylaminopurine (6-BA, a synthetic type of CTK) and CYC enhanced the inducing effect of CYC, whereas exogenous application of lovastatin (a synthetic type of inhibitor of CTK biosynthesis) or ABA and CYC weakened the promoting effect of CYC. These results collectively revealed that the stimulation of bud growth by CYC might involve CTK biosynthesis and signalling, including genes CKX1 and ARR3/9, which provided a direction for further study of the branching promoting mechanism of CYC.
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Hewicker-Trautwein, M., R. v. Wasielewsky, R. Mischke, and R. Höinghaus. "Immunzytologische Charakterisierung von gastrointestinalen Tumoren und deren Metastasen beim Hund." Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere 34, no. 01 (2006): 29–34. http://dx.doi.org/10.1055/s-0037-1622506.
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Zusammenfassung Gegenstand und Ziel: Das Ziel dieser Studie war die Überprüfung der kommerziell erhältlichen (antihumanen) Antikörper CK7 und CK20 an zytologischen Präparaten von gastrointestinalen Geweben des Hundes. Material und Methoden: Von insgesamt 27 Hunden (ein gesundes Tier) wurden zytologisch aufbereitete Tupfpräparate von gesundem Gewebe der Gallengänge, des Pankreas, der Magenund Darmschleimhaut sowie von Neoplasien (neun Magenkarzinome, sechs Dünndarmkarzinome, vier Rektumpolypen, drei Rektumkarzinome, ein Gallengangsadenom, zwei Gallengangskarzinome, ein Pankreaskarzinom), davon ausgehenden Organmetastasen (n = 5) und Lymphknoten (n = 32) gewonnen. Die zytologischen Präparate wurden immunzytologisch mit den Antikörpern CK7 und CK20 gefärbt. Ergebnisse: Die immunzytologische Reaktion in normaler Magen-, Dünnund Dickdarmschleimhaut war durchgehend CK20-positiv und CK7-negativ. In den von der Magen- und Darmschleimhaut ausgehenden Neoplasien und deren Metastasen konnte neben der konstanten CK20-Expression in vielen Fällen auch eine CK7-Expression festgestellt werden. Die gesunden Gewebe und Neoplasien des Pankreas und der Gallengänge und davon ausgehende Metastasen zeigten immunzytologisch ein konstant CK20-negatives und CK7-positives Reaktionsmuster. Die in dieser Studie dargestellte oft CK7-positive Reaktion in Neoplasien der Magenund Darmschleimhaut des Hundes wurde beim Menschen nur für die von der Magenschleimhaut ausgehenden Veränderungen beschrieben. Hiervon abgesehen entsprechen die festgestellten Reaktionsmuster den Verhältnissen beim Menschen. Klinische Relevanz: Die erarbeiteten Reaktionsmuster können insbesondere bei der diagnostischen Eingrenzung von Primärtumoren unbekannter Herkunft und Fernmetastasen wertvolle Dienste leisten.
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P. Keramida, N. N. Souris, A. G. Bo, E. "Numerical Modeling of Radiative Heat Transfer in Integrated CFD Fire Modeling." Journal of Applied Fire Science 9, no. 1 (October 1, 1999): 3–19. http://dx.doi.org/10.2190/9jwq-ckn7-wa7h-ee8h.
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Andrade, Victor Manoel. "Dreaming as a primordial state of the mind: The clinical relevance of structural faults in the body ego as revealed in dreaming." International Journal of Psychoanalysis 88, no. 1 (February 2007): 55–74. http://dx.doi.org/10.1516/80lu-v6x1-3klp-ck47.
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Zielinska, Dorota. "Drawing on Technical Writing Scholarship for the Teaching of Writing to Advanced Esl Students—A Writing Tutorial." Journal of Technical Writing and Communication 33, no. 2 (April 2003): 125–39. http://dx.doi.org/10.2190/daya-ckxa-ldc2-f95y.
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The article outlines the technical writing tutorial (TWT) that preceded an advanced ESL writing course for students of English Philology at the Jagiellonian University. Having assessed the English skills of those students at the end of the semester, we found a statistically significant increase in the performance of the students who had taken the TWT in comparison to the control group who spent the time of TWT doing more traditional exercises. This result indicates that technical writing books and journals should be considered as an important source of information for teachers of writing to ESL students.
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Ming, Chen. "A Shared Multi-Media Design Environment for Concurrent Engineering over the Internet." Concurrent Engineering: Research and Applications 9, no. 1 (March 1, 2001): 55–63. http://dx.doi.org/10.1106/dycb-ckxw-vn6l-6ket.
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Kemp, Bryan, Rodney Adkins, and Lilli Thompson. "Aging with a Spinal Cord Injury: What Recent Research Shows." Topics in Spinal Cord Injury Rehabilitation 10, no. 2 (October 2004): 175–97. http://dx.doi.org/10.1310/ln1a-ck97-33ac-qff3.
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Michael, Youle. "Selected Topics from the XI International HIV Drug Resistance Workshop, Seville, and the XIV International AIDS Conference, Barcelona." HIV Clinical Trials 3, no. 6 (December 2002): 503–10. http://dx.doi.org/10.1310/rcl4-lbxl-ckxa-btjh.
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Kinzie, Mable B., Howard J. Sullivan, and Richard L. Berdel. "Motivational and Achievement Effects of Learner Control over Content Review within CAI." Journal of Educational Computing Research 8, no. 1 (February 1992): 101–14. http://dx.doi.org/10.2190/2ewh-j2f1-ck87-09nr.
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This study investigated the effects of learner and program control over content review within science computer-assisted instruction (CAI). Ninth grade subjects completed learner and program controlled CAI and a unit posttest. Continuing motivation for learner and program control was measured by giving half the subjects a choice of control type for a subsequent session. Results indicated that program control resulted in better posttest performance for males. For females, learner control provided a nonsignificant advantage. This sex difference is discussed relative to a possible differential effort on the part of males and females. Results also reveal significant differences in continuing motivation for learner control, with subjects returning more frequently to learner control than program control in the second session. Strong student preferences for instruction via computers were also noted.
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JOHNSTON, HEATHER, W. DARYL LINDSAY, and FRED PHILLIPS. "Undetected Deviations in Tests of Controls: Experimental Evidence of Nonsampling Risk*." Canadian Accounting Perspectives 2, no. 2 (November 2003): 113–34. http://dx.doi.org/10.1506/ckx0-8fbf-9ngf-ccrq.
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Zhao, Dandan, Hirokazu Ogawa, Xiang Wang, Gregory S. Cameron, Darric E. Baty, Jeffrey S. Dlott, and Douglas A. Triplett. "Oxidized Low-Density Lipoprotein and Autoimmune Antibodies in Patients With Antiphospholipid Syndrome With a History of Thrombosis." American Journal of Clinical Pathology 116, no. 5 (November 2001): 760–67. http://dx.doi.org/10.1309/1ryq-q2aj-ckf7-ycde.
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Lin, Yi, Yaoying Zeng, Jingfang Di, and Shan Zeng. "Murine CD200+CK7+ trophoblasts in a poly (I:C)-induced embryo resorption model." Reproduction 130, no. 4 (October 2005): 529–37. http://dx.doi.org/10.1530/rep.1.00575.
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Cytokeratin 7 (CK7) is currently regarded as the best marker for trophoblast cells, while CD200 (OX-2), known as ‘tolerance signal’, plays an important role in normal pregnancy. In this study, the status of CD200 expression was investigated in BALB/c × C57BL/6 and BALB/c × BALB/c mating combinations designed as allogeneic and syngeneic murine models of induced embryo resorption, in which the resorption rate was boosted by an i.p. injection of poly (I:C), a synthetic double-stranded RNA. The percentage of CD200+cells in the CK7+cell population (CD200+CK7+percentage) and the absolute number of these cells were determined with flow cytometry, using trophoblast cells collected at day 8.5 and day 13.5 of gestation. The potential effect of poly (I:C) on CD200 expression was also evaluated by detecting the CD200+CK7+percentage in trophoblast cells incubated in the presence or absence of poly (I:C),in vitro. The distribution pattern of CD200+cells at the feto–maternal interface was evaluated by immunocytochemical examination. When 104cells were analyzed at day 8.5 of gestation in each case, no significant difference was observed between the poly (I:C)-treated group and the control PBS group either in the CD200+CK7+percentage or in the absolute number of these cells. Similar results were observed both in BALB/c × C57BL/6 mice and in BALB/c × BALB/c mice. However, the CD200+CK7+percentage was significantly decreased in the poly (I:C)-treated group when evaluated at day 13.5 of gestation. Accordingly, a dramatically elevated rate of embryo resorption was observed at this time point of pregnancy after the administration of poly (I:C). In addition, the CD200+CK7+percentage was significantly lower in trophoblast cells incubated with poly (I:C) at a certain concentration,in vitro, while histocytochemical examination showed the CD200+cells mainly scattered in placental tissue adjacent to the interface of the placenta and uterus. This indicates that sufficient expression of the CD200 molecule on CK7+cells at the feto–maternal interface may be necessary for the maintenance of embryos during pregnancy in this rodent model, while poly (I:C) administration may increase embryo resorption, at least partially via direct inhibition of CD200 expression on CK7+cells.
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Ivkovic-Kapicl, Tatjana, Milana Panjkovic, Ivan Nikolic, Dragana Djilas-Ivanovic, and Slavica Knezevic-Usaj. "Expression of cytokeratins 5/6 and cytokeratin 17 in invasive breast carcinoma." Vojnosanitetski pregled 69, no. 12 (2012): 1031–38. http://dx.doi.org/10.2298/vsp1212031i.
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Background/Aim. Cytokeratins (CK) 5/6 and 17, myoepithelial markers, are also expressed in a proportion of breast carcinomas. Breast carcinomas expressing basal epithelium cytokeratins constitute a tumor subgroup that shows common but heterogeneous morphological, genetical, and immunophenotypical features and is associated with poor clinical outcome. The aim of this study was to determine the incidence of basal expression of cytokines CK5/6 and CK17 in the tested samples of ductal invasive breast cancers, as well as to test the presence of a correlation of tumor expression of basal cytokines and clinicopathological prognostic factors: age, the level of histological differentiation, hormone receptor status, HER2 (human epidermal prowth factor receptor 2) protein expresion and HER2 gene amplification in tumorous tissue. Methods. Immunohistochemistry (IHC) was used to evaluate the CK5/6 and CK17 status of 121 ductal invasive breast cancers. The results thus obtained were compared with clinicopathological characteristics. Results. From the 117 analyzed tumor specimens, 22% and 30% were immunohistochemically positive for CK5/6 and CK17, respectively. Basal cytokeratins showed significant inverse relationship with estrogen and progesterone receptor status and HER2 protein expression. CK5/6 and CK17 immunoreactivities were directly associated with triple-negative phenotype and higher histological grade. Conclusion. Our findings are similar to reports that tumours expression of basal cytokeratins are correlated with adverse pathological parameters. Given the limited number of emerging therapeutic targets in these tumors, routine IHC identification of basal-like subtype as a poor prognostic group of breast cancer could be based on the expression of basal CKs.
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Hassan, Sherif S., Mahmoud A. Attia, Alaa M. Attia, Reda A. Nofal, and Adel Fathi. "Distribution of Cytokeratin 17 in the Parenchymal Elements of Rat’s Submandibular Glands Subjected to Fractionated Radiotherapy." European Journal of Dentistry 14, no. 03 (June 26, 2020): 440–47. http://dx.doi.org/10.1055/s-0040-1713705.
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Abstract Objectives The aim of this research was to study the intensity of cytokeratin 17 (CK17) in the parenchymal elements of rat’s submandibular salivary glands subjected to fractionated radiotherapy regimen that used for treatment of head and neck malignancy. Materials and Methods Twenty male albino rats were divided into two equal groups (normal and irradiated). The irradiated group received a radiation dose of 5 Grays daily for 5 days using therapeutic X-ray beam. Six months later, submandibular gland was dissected out and prepared for both histological and immunohistochemical studies. Results Submandibular gland of irradiated group showed two different types of histological alterations. The first alteration showed severe gland atrophy replaced by either fibrous or fatty tissues. In some sections, the gland exhibited proliferating activity in the form of profuse amounts of mitotic figures. Immunohistochemical examination of control glands displayed a mild cytoplasmic expression of CK17 of duct cells as well as serous acini. The staining pattern was either diffused or concentrated at the basal part of the cell with negative expression at its apical part. Statistical Analysis Expression of CK17 in submandibular gland of irradiated group displayed a highly significant differences (P < 0.001) in both intercalated and striated ducts. Many serous acini displayed a highly significant differences (P < 0.001) whereas, mucous acini were negatively stained. Conclusions The intensity and diffusion of CK17 expression in our results foretell the pathological effect of radiotherapy on the intermediate filaments of salivary gland parenchyma that interfered with production and/or secretion of saliva leading to xerostomia.
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Pieper, Jason B., Adam W. Stern, Suzette M. LeClerc, and Karen L. Campbell. "Coordinate expression of cytokeratins 7 and 14, vimentin, and Bcl-2 in canine cutaneous epithelial tumors and cysts." Journal of Veterinary Diagnostic Investigation 27, no. 4 (July 2015): 497–503. http://dx.doi.org/10.1177/1040638715594115.
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Forty-seven canine cutaneous epithelial tumors and cysts were examined to determine coordinate expression of cytokeratins 7 (CK7) and 14 (CK14), vimentin, and Bcl-2 using commercially available antibodies. Within non-affected normal skin adjacent to tumors or cysts, CK7 expression was observed in luminal cells in apocrine glands; CK14 expression was observed in the stratum basale, stratum spinosum, stratum granulosum, basal layer of outer root sheath, sebaceous glands, and myoepithelial cells of apocrine glands; vimentin expression was observed in dermal papilla and scattered non-epithelial cells within the epidermis; and Bcl-2 expression was observed in scattered non-epithelial cells in the epidermis and some apocrine glands. The pattern of expression of CK7 and CK14 in cases of adenocarcinoma of the apocrine gland of the anal sac (CK7+/CK14–) and hepatoid gland tumors (CK7–/CK14+) may prove useful for diagnostic purposes. Loss of expression of CK14 and vimentin, identifying myoepithelial cells, was observed in apocrine and ceruminous adenocarcinomas. Differences in patterns of expression of Bcl-2 were observed between infundibular keratinizing acanthomas compared to trichoepitheliomas.
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Shablii, V., M. Kuchma, H. Svitina, I. Skrypkina, P. Areshkov, V. Kyryk, T. Bukreieva, V. Nikulina, Iu Shablii, and G. Lobyntseva. "High Proliferative Placenta-Derived Multipotent Cells Express Cytokeratin 7 at Low Level." BioMed Research International 2019 (July 15, 2019): 1–13. http://dx.doi.org/10.1155/2019/2098749.
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The purpose of this study was to investigate the immunophenotypes and gene expression profile of high proliferative placenta-derived multipotent cells (PDMCs) population at different stages of culture. We demonstrated that the colonies resulting from single cells were either positive or negative for CK7, whereas only PDMC clones with weak CK7 expression (CK7low-clones) were highly proliferative. Interestingly, vimentin positive (Vim+) placental stromal mesenchymal cells did not express CK7 in situ, but double CK7+Vim+ cells detection in tissue explants and explants outgrowth indicated CK7 inducible expression in vitro. PCNA presence in CK7+Vim+ cells during placental explants culturing confirmed belonging of these cells to proliferative subpopulation. Transcription factors CDX2 and EOMES were expressed in both CK7low-clones and subset of stromal mesenchymal cells of first-trimester placental tissue in situ. Meanwhile, CK7low -clones and stromal mesenchymal cells of full-term placental tissue in situ expressed ERG heterogeneously. SPP1, COL2A1, and PPARG2 mesodermal-related genes expression by CK7low-clones additionally confirms their mesenchymal origin. Inherent stem cell-related gene expression (IFTM3, POU5F1, and VASA) in CK7low-clones might indicate their enrichment for progenitors. Finally, in CK7low-clones we observed expression of such trophoblast-associated genes as CGB types I and II, fusogenic ERVW-1, GCM1, and GATA3. Thus, our results indicate that PDMCs acquired the representative immunophenotype signature under culture conditions.
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White, Nicole, Manal Gabril, Gershon Ejeckam, Maria Mathews, John Fardy, Fady Kamel, Jules Doré, and George M. Yousef. "Barrett’s Esophagus and Cardiac Intestinal Metaplasia: Two Conditions within the Same Spectrum." Canadian Journal of Gastroenterology 22, no. 4 (2008): 369–75. http://dx.doi.org/10.1155/2008/243254.
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BACKGROUND: Immunostaining for cytokeratin 7 (CK7) and cytokeratin 20 (CK20) has a characteristic pattern in Barrett’s esophagus (BE), but reports regarding its sensitivity and specificity are inconsistent. Intestinal metaplasia of the gastric cardia (CIM) is histologically similar to BE, but with no abnormal endoscopic findings.OBJECTIVES: To evaluate the sensitivity and specificity of a semi-quantitative CK7/CK20 immunostaining pattern for the diagnosis of BE, and to further elucidate the pathogenesis of CIM.METHODS: Tissues were examined by hematoxylin and eosin and periodic acid schiff/alcian blue stains, and then were immunostained with CK7 and CK20 antibodies. Correlations with other clinical parameters were statistically analyzed.RESULTS: When values were revised based on follow-up data and auxiliary testing, all BE cases (100%) displayed the characteristic BE CK7/CK20 immunostaining pattern, compared with 66% of CIM cases. In the subgroup of patients who were endoscopically and immunohistochemistry-positive but histologically negative, all patients except for one had documented BE when clinical history, auxiliary testing and follow-up were evaluated. There were no statistically significant differences between BE and CIM regardingHelicobacter pyloriinfection or the type of metaplasia (complete versus incomplete). The sensitivity of the CK7/CK20 pattern reached 100% in the subgroup of CIM patients with a history of acid reflux. Of 26 cases of CIM where follow-up was available, four cases (15%) progressed to BE, and one developed dysplasia. All four cases showed the BE pattern of CK7/CK20 staining and were negative forH pyloriinfection.CONCLUSIONS: A semiquantitative CK7/CK20 pattern can be used to confirm BE even in the absence of histological evidence. The subgroup of CIM with acid reflux may develop into BE and may need closer follow-up.
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Dabravolski, Siarhei A., and Stanislav V. Isayenkov. "Evolution of the Cytokinin Dehydrogenase (CKX) Domain." Journal of Molecular Evolution 89, no. 9-10 (November 8, 2021): 665–77. http://dx.doi.org/10.1007/s00239-021-10035-z.
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KIRN, TIMOTHY F. "CK7 Stain Aids Mohs in Extramammary Paget's." Skin & Allergy News 38, no. 2 (February 2007): 14. http://dx.doi.org/10.1016/s0037-6337(07)70021-9.
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Neri, Giuseppe, Giovanni Arpa, Camilla Guerini, Federica Grillo, Marco Vincenzo Lenti, Paolo Giuffrida, Daniela Furlan, et al. "Small Bowel Adenocarcinomas Featuring Special AT-Rich Sequence-Binding Protein 2 (SATB2) Expression and a Colorectal Cancer-Like Immunophenotype: A Potential Diagnostic Pitfall." Cancers 12, no. 11 (November 19, 2020): 3441. http://dx.doi.org/10.3390/cancers12113441.
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Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn’s disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7−/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7−/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7−/CK20− or CK7−/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20− or CK7+/CK20+ cancers (p = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7−/CK20− cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.
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Jiang, Jiazhong, Thomas M. Ulbright, Cheryl Younger, Katya Sanchez, David G. Bostwick, Michael O. Koch, John N. Eble, and Liang Cheng. "Cytokeratin 7 and Cytokeratin 20 in Primary Urinary Bladder Carcinoma and Matched Lymph Node Metastasis." Archives of Pathology & Laboratory Medicine 125, no. 7 (July 1, 2001): 921–23. http://dx.doi.org/10.5858/2001-125-0921-cacipu.
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Abstract Background.—Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. Objective.—To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. Design.—We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. Results.—In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. Conclusions.—CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.
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Miyaoka, Masashi, Kazuhito Hatanaka, Masayuki Iwazaki, and Naoya Nakamura. "CK7/CK20 Double-Negative Pulmonary Enteric Adenocarcinoma With Histopathological Evaluation of Transformation Zone Between Enteric Adenocarcinoma and Conventional Pulmonary Adenocarcinoma." International Journal of Surgical Pathology 26, no. 5 (February 7, 2018): 464–68. http://dx.doi.org/10.1177/1066896918756737.
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We report a rare case of pulmonary enteric adenocarcinoma (PEA) exhibiting a immunohistochemical feature of CK7/CK20 double-negativity by evaluating the transformation zone between PEA and conventional pulmonary adenocarcinoma (CPA). A 75-year-old man was found to have a mass, 40 mm in diameter, in the right lower lobe on chest computed tomography, and underwent right lower lobectomy. Histologically, the tumor was composed of a PEA and CPA component. The dominant PEA component had medium to large complex glands with tall columnar cells with eosinophilic cytoplasm and brush-border. The CPA component comprised small to medium glands with cuboidal cells. Moreover, intermediate glands (INT), which had cuboidal to tall columnar cells, with morphological features between PEA and CPA, was also observed in the transformation area. Immunohistochemically, the PEA component was negative for CK7, CK20, and TTF-1, and positive for CDX2 and SATB2 (weak): the CPA component was negative for CK20, CDX2, and SATB2, and positive for CK7 and TTF-1: the INT were negative for SATB2, with intermingled positive signals for CK7, CK20, TTF-1, and CDX2. The final diagnosis was PEA based on the CPA component and not colorectal carcinoma. To distinguish CK7-negative PEA from metastatic colorectal carcinoma, careful examination for a CPA component is very useful along with clinical information. There are no reports that discuss about process of oncogenesis, de novo sequence or transformation from CPA of PEA. This is the first reported case of CK7/CK20 double-negative PEA, with analysis of the transformation zone between PEA and CPA components.
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Park, Seog-Yun, Baek-Hee Kim, Jung-Ho Kim, Sun Lee, and Gyeong Hoon Kang. "Panels of Immunohistochemical Markers Help Determine Primary Sites of Metastatic Adenocarcinoma." Archives of Pathology & Laboratory Medicine 131, no. 10 (October 1, 2007): 1561–67. http://dx.doi.org/10.5858/2007-131-1561-poimhd.
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Abstract Context.—Although identification of the primary tumor in patients with metastatic adenocarcinoma has a profound clinical impact, diagnosing the organ of origin is frequently difficult. Because none of the individual immunohistochemical markers used for tissue identification are both site specific and site sensitive, multiple markers are needed to improve the prediction of primary sites. Objective.—To develop an effective approach to immunohistochemically evaluate metastatic adenocarcinoma for the assignment of a likely primary site of origin. Design.—Expression profiles of CDX2, cytokeratin (CK) 7, CK20, thyroid transcription factor 1 (TTF-1), carcinoembryonic antigen (CEA), MUC2, MUC5AC, SMAD4, estrogen receptor (ER), and gross cystic disease fluid protein 15 (GCDFP-15) were generated in adenocarcinomas from 7 primary sites, followed by construction of a decision tree and design of multiple-marker panels. Expression of these markers was evaluated immunohistochemically in 314 primary adenocarcinomas (50 cases each of colorectal, gastric, lung, pancreatic, bile duct, and breast, and 14 cases of ovarian origin) using the tissue array method. Results were validated using 60 cases of metastatic adenocarcinoma with known primaries. Results.—Organ-specific immunostaining profiles using multiple markers provided high sensitivity, specificity, and positive predictive value in detecting primary adenocarcinomas, as follows: colorectal, TTF-1−/CDX2+/CK7−/CK20+ or TTF-1−/CDX2+/CK7−/CK20−/(CEA+ or MUC2+); ovarian, CK7+/MUC5AC+/TTF-1−/CDX2−/CEA−/GCDFP-15−; breast, GCDFP-15+/TTF-1−/CDX2−/CK7+/CK20− or ER+/ TTF-1−/CDX2−/CK20−/CEA−/MUC5AC−; lung, TTF-1+ or TTF-1−/CDX2−/CK7+/CK20−/GCDFP-15−/ER−/CEA−/ MUC5AC−; pancreaticobiliary, TTF-1−/CDX2−/CK7+/ CEA+/MUC5AC+; and stomach, TTF-1−/CDX2+/CK7+/ CK20−. Overall, these combined phenotypes correctly predicted the tester samples (metastatic adenocarcinomas with known primaries) in 75% of cases. Conclusions.—Determination of tissue-specific immunostaining profiles is valuable in the diagnostic differentiation of metastatic adenocarcinomas from seven common primary sites and should help to correctly predict the organ of primary tumor origin.
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Buntić, A. V., M. D. Pavlović, S. S. Šiler-Marinković, and S. I. Dimitrijević-Branković. "Biological treatment of colored wastewater by Streptomyces fulvissimus CKS 7." Water Science and Technology 73, no. 9 (February 8, 2016): 2231–36. http://dx.doi.org/10.2166/wst.2016.078.
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This study aims to investigate the biological processes related to the biodegradable potential of growing microbial cells for contaminated water treatment. Thus, the use of the Streptomyces fulvissimus CKS 7 (CKS7) has been evaluated for decolorizing efficiency of a solution containing a cationic triphenylmethane dye, crystal violet. The color reduction was monitored by UV–Vis spectroscopic analysis, through changes in their absorption spectrum and comparing the results with those of the respective controls. It was found that the CKS7 performed well and reached up to 100% effectiveness. The required process parameters have been apparently mild and include the reaction temperature of 27–30 °C, 10% inoculum size, under shaking conditions, whereas the time course of decolorization had been concentration dependent. A possible mechanism for removing dye from the working medium was accomplished in two steps: the binding of the dye on the bacterial cell surface, in addition to the dye biodegradation by the bacterial intracellular enzymes. After one cycle of the complete dye removal, the adapted culture was successfully reused for the same purpose. The phytotoxicity analysis revealed that non-toxic compounds were present in decolorized medium, indicating that the CKS7 bacteria seem to be a promising application for contaminated water treatment.
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Kurokawa, I., S. Nishijima, K. Kusumoto, H. Senzaki, N. Shikata, and A. Tsubura. "Immunohistochemical Study of Cytokeratins in Hidradenitis Suppurativa (Acne Inversa)." Journal of International Medical Research 30, no. 2 (April 2002): 131–36. http://dx.doi.org/10.1177/147323000203000205.
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In 14 cases of hidradenitis suppurativa, cytokeratin (CK) expression was studied immunohistochemically, using six anti-keratin antibodies against CK1, CK10, CK14, CK16, CK17 and CK19, respectively. The draining sinus tract epithelium of hidradenitis suppurativa lesions was divided into three components: infundibular-like keratinized epithelium (type A), non-infundibular keratinized epithelium (type B), and non-keratinized epithelium (type C). In type A samples, CK17 (which is found in normal infundibulum) was not detected, suggesting fragility of this epithelial type. Keratin expression in types B and C epithelia was similar to that observed in the outer root sheath in normal hair follicles. Our results suggest that the draining sinus epithelium may possess characteristics of fragility, undifferentiation and hyperproliferation, as shown with CK expression.