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Hum Pathol. 2017 Sep;67:30-36. doi: 10.1016/j.humpath.2017.03.020. Epub 2017 Apr 13.

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

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Institute of Pathology, Charité University Hospital, Berlin 10117, Germany. Electronic address:
Institute of Pathology, Charité University Hospital, Berlin 10117, Germany; Tumor Bank Ovarian Cancer Network (TOC) Berlin 10117, Germany.
Tumor Bank Ovarian Cancer Network (TOC) Berlin 10117, Germany; Department of Gynecology, Charité University Hospital, Berlin 10117, Germany.
Institute of Pathology, Charité University Hospital, Berlin 10117, Germany.


High-grade serous ovarian carcinoma remains one of the most lethal malignancies in women. For histopathologic differentiation from mesothelioma cytokeratin, 5/6 immunohistochemistry is widely used. Another preferred marker for differential diagnosis to mesothelioma is estrogen receptor α (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. Most 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. Sixty-seven (31%) were entirely negative. No correlation of cytokeratin immunoreactivity score (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 cytokeratin 5/6 IRS=12 and ER-α negativity resulted in a significant negative prognostic marker (overall survival: P=.003 and 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.


Biomarker analysis; Cytokeratin 5/6; ER-α; High-grade serous; Ovarian carcinoma; Prognostic parameter

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