Subcellular localization of p27^kip1 expression predicts poor prognosis in human ovarian cancer

Purpose: The cyclin-dependent kinase inhibitor p27^kip1 regulates cellular progression from G₁ to S phase. Several studies have shown that loss of p27^kip1 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 p27^kip1 was first assessed by Western blotting in nuclear and cytoplasmic extract from 13 cases of ovarian carcinoma. Subcellular localization of the p27^kip1 protein was evaluated using tissue microarrays containing 421 cases of ovarian carcinoma. Results: The presence of p27^kip1 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 p27^kip1 predicts poorer prognosis in ovarian carcinoma, particularly in late-stage disease.