The combined evaluation of p27Kip1 and Ki-67 expression provides independent information on overall survival of ovarian carcinoma patients.

Abstract

Considering the limited and controversial information on the significance of the cyclin-dependent kinase inhibitor p27Kip1 in ovarian cancer, we conducted a retrospective investigation to clarify the relationships of this protein to proliferation rate, clinicopathologic variables, and prognosis of epithelial ovarian tumors. Paraffin-embedded tissue from 43 ovarian tumors of low malignant potential (LMP) and 80 primary ovarian adenocarcinomas was stained immunohistochemically for p27Kip1, Ki-67 antigen (a marker of cell proliferation), and p53 protein. Expression of these markers was correlated with clinicopathologic features and with overall survival of patients with adenocarcinomas. p27Kip1 levels were significantly higher in LMP tumors as well as in low-grade, early-stage, slowly proliferating adenocarcinomas and those associated with minimal residual disease (P < 0.001). Decreased p27Kip1 expression was related to poor overall survival on its own (P = 0.0304) and, when combined, to increased proliferation rate (P = 0.0232). More importantly, in multivariate analysis, p27Kip1/Ki-67 status was independently related to survival (P = 0.040) along with histologic type and FIGO stage. Decreased p27Kip1 expression is related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas and is a major player in cell cycle control in these neoplasms. On the contrary, deregulation of the protein does not seem to participate in the pathogenesis of LMP tumors. Furthermore, combined p27Kip1/Ki-67 expression is a better prognostic marker than expression of p27Kip1 or Ki-67 alone and supplements the prognostic information gained from traditional prognosticators.