Subcellular localization of p27kip1 expression predicts poor prognosis in human ovarian cancer

Abstract

Purpose: The cyclin-dependent kinase inhibitor p27kip1 regulates cellular progression from G1 to S phase. Several studies have shown that loss of p27kip1 protein expression is associated with disease progression in various malignancies. The purpose of this study was to evaluate the subcellular localization of this cyclin-dependent kinase inhibitor in a large cohort of primary ovarian carcinomas and compare the results with clinicopathologic variables and overall survival. Experimental Design: Subcellular localization of p27kip1 was first assessed by Western blotting in nuclear and cytoplasmic extract from 13 cases of ovarian carcinoma. Subcellular localization of the p27kip1 protein was evaluated using tissue microarrays containing 421 cases of ovarian carcinoma. Results: The presence of p27kip1 in the cytoplasm regardless of the nuclear stain correlated strongly with late-stage disease (P < 0.03), extent of cytoreduction (P = 0.03), and shorter disease-specific survival (P < 0.0001). Conclusion: Cytoplasmic localization of p27kip1 predicts poorer prognosis in ovarian carcinoma, particularly in late-stage disease.