Emi1 protein accumulation implicates misregulation of the anaphase promoting complex/cyclosome pathway in ovarian clear cell carcinoma.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Ines GütgemannTeri A Longacre

Abstract

Clear cell carcinoma is a clinically and pathologically distinct entity among surface epithelial ovarian neoplasms, recognized for its resistance to standard platinum-based chemotherapy at advanced stage disease and poor prognosis. Despite advances in our understanding of the biology of other surface epithelial ovarian neoplasms, very little is known about the molecular genetic mechanisms that are involved in clear cell tumorigenesis. Early mitotic inhibitor-1 (Emi1) protein is a key cell cycle regulator, that promotes S-phase and mitotic entry by inhibiting the anaphase promoting complex. In cell culture systems, overexpression of Emi1 leads to tetraploidy and genomic instability, especially in the absence of normal p53 function. We investigated Emi1 protein expression in ovarian neoplasms using a tissue microarray constructed from 339 primary ovarian surface epithelial (serous, endometrioid, clear cell, and mucinous) and peritoneal (serous) neoplasms, stromal and mesenchymal tumors, germ cell tumors, and normal ovarian tissue. Significant overexpression of Emi1 protein was present in 82% (27/33) clear cell carcinoma, including one borderline tumor in a diffuse, granular cytoplasmic and perinuclear staining pattern, independen...Continue Reading

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