Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.