p27(Kip1) expression is associated with clinical outcome in advanced epithelial ovarian cancer: Multivariate analysis

Few biological parameters have been shown to have a prognostic role in pati ents with advanced ovarian cancer. p27(Kip1) is a cyclin-dependent kinase i nhibitor, and its loss may contribute to tumor progression. We determined w hether p27(Kip1) protein expression in advanced ovarian cancer could be ass ociated with prognosis. p27(Kip1) status was assessed by immunohistochemica l analysis of tissue sections from primary tumors of 99 patients with stage s III-IV ovarian carcinoma and was analyzed in relation to clinicopathologi cal variables, time to progression (TTP), and overall survival (OS), p27(Ki p1) 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 = 0.0 004) and decreased OS (P = 0.0302), The 5-year TTP rate in p27-positive pat ients was 50% versus 11% in p27-negative patients. p27-positive cases showe d a 5-year OS rate of 53% compared with 43% of p27-negative cases. In multi variate analysis, p27 expression was an independent predictor of progressio n of disease (P = 0.0009) and survival (P = 0.0032) when considered togethe r 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, p 27 immunoreactivity can be used to predict progression of disease and survi val in patients with advanced epithelial ovarian cancer and therefore may r epresent a new prognostic marker.