Cytokeratin 5/6 expression, prognosis and association with ER-α in high-grade serous ovarian carcinoma

Publication date: Available online 13 April 2017
Source:Human Pathology
Author(s): Eliane Tabea Taube, Carsten Denkert, Jalid Sehouli, Ulrike Unger, Catarina Alisa Kunze, Jan Budczies, Manfred Dietel, Elena Braicu, Silvia Darb-Esfahani
High-grade serous ovarian carcinoma remains one of the most lethal malignancies in females. For histopathological differentiation from mesothelioma cytokeratin, 5/6 immunohistochemistry is widely used. Another preferred marker for differential diagnosis to mesothelioma is ER-α. In this study, we determined the rate of cytokeratin 5/6 positive cells in primary high-grade serous carcinoma. A cohort of 215 patients with high-grade serous ovarian carcinoma was evaluated immunohistochemically for the protein expression of cytokeratin 5/6. The majority of tumors demonstrated, at least partly positive for cytokeratin 5/6 (n=148, 68.3%), showing different staining patterns from scattered stained cells to a diffuse staining, at times with a distinctive tumor-stroma border motif. 67 (31%) were entirely negative. No correlation of cytokeratin IRS with conventional staging parameters could be demonstrated. From the different IRS values for cytokeratin, 5/6 IRS=12 (n=6, 2.9%) seemed to indicate a worse prognosis, albeit not statistically significant. An association with ER-α expression could not be detected but the combination of CK5/6 IRS=12 and ER-α negativity resulted in a significant negative prognostic marker (overall survival P=.003 und progression free survival P<.0001). We substantiate cytokeratin 5/6 protein expression as a frequent feature of high-grade serous ovarian carcinoma with various staining patterns, an important fact for the routine differential diagnosis with mesothelioma. Furthermore, cytokeratin 5/6 in combination with ER-α proved to be a negative prognostic marker, wherefore we suggest further investigation of its biological significance and possible manifestation of a basal differentiation.



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