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p27^Kip1 Expression Is Associated with Clinical Outcome in Advanced Epithelial Ovarian Cancer: Multivariate Analysis¹

Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107 [V. M., B. P., S. L., J. P., A. G.]; Department of Obstetrics and Gynecology, Catholic University, Rome 00168, Italy [G. F., F. F., S. M., G. S.]; and Department of Surgical Pathology, Catholic University, Rome 00168, Italy [G. Z.]

Few biological parameters have been shown to have a prognostic role in patients with advanced ovarian cancer. p27^Kip1 is a cyclin-dependent kinase inhibitor, and its loss may contribute to tumor progression. We determined whether p27^Kip1 protein expression in advanced ovarian cancer could be associated with prognosis. p27^Kip1 status was assessed by immunohistochemical analysis of tissue sections from primary tumors of 99 patients with stages III–IV ovarian carcinoma and was analyzed in relation to clinicopathological variables, time to progression (TTP), and overall survival (OS). p27^Kip1 expression was detected in 47 (47%) of the 99 patients. p27 expression did not correlate with any of the classical clinicopathological parameters. Loss of p27 protein was significantly associated with a short TTP (P = 0.0004) and decreased OS (P = 0.0302). The 5-year TTP rate in p27-positive patients was 50% versus 11% in p27-negative patients. p27-positive cases showed a 5-year OS rate of 53% compared with 43% of p27-negative cases. In multivariate analysis, p27 expression was an independent predictor of progression of disease (P = 0.0009) and survival (P = 0.0032) when considered together with stage of disease, presence of ascites, and residual tumor at surgery. Loss of p27^Kip1 conferred poor prognosis independently of proliferative index, as assessed by proliferating cell nuclear antigen immunostaining. p27 immunoreactivity can be used to predict progression of disease and survival in patients with advanced epithelial ovarian cancer and therefore may represent a new prognostic marker.

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