Alteration of cell-cycle regulation in epithelial ovarian cancer

Abstract

In spite of the clinical importance of epithelial ovarian cancer (EOC), little is known about the pathobiology of its precursor lesions and progression. Regulatory mechanisms of the cell cycle are mainly composed of cyclins, cyclin-dependent kinases (CDK), and CDK inhibitors. Alteration of these mechanisms results in uncontrolled cell proliferation, which is a distinctive feature of human cancers. This review describes the current state of knowledge about the alterations of cell-cycle regulations in the context of p16–cyclin D1–CDK4/6–pRb pathway, p21–p27–cyclin E–CDK2 pathway, p14–MDM2–p53 pathway, and ATM–Chk2–CDC25 pathway, respectively. Recent evidence suggests that ovarian cancer is a heterogenous group of neoplasms with several different histologic types, each with its own underlying molecular genetic mechanism. Therefore, expression of cell cycle regulatory proteins should be tested separately according to each histologic type. In serous ovarian carcinoma, high expression of p16, p53, and p27 and low expression of p21 and cyclin E were shown. In addition, this review focuses on the prognostic significance of cell cycle–regulating proteins in EOC. However, it is difficult to compare the results from different groups due to diverse methodologies and interpretations. Accordingly, researchers should establish standardized criteria for the interpretation of immunohistochemical results.