Loss of p27(KIP1) expression correlates with tumor grade and with reduced disease-free survival in primary superficial bladder cancers

p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. We previously reported a deregulated expression of p27(Kip1) in a series of human cancer cell lints and in primary breast and colon cancers. Moreover, p27(Kip1) has been reported as an important prognostic factor in primary lung, breast, colon, and prostate cancers. In this study, we evaluated the prognostic value of p27(Kip1) in a series of 96 superficial (pTa-1) human bladder carcinomas. High ( >50 % positive cells), moderate (25-50 %), and low (<25 %) p27(Kip1) staining was observed in 39 (41%), 19 (20%), and 38 (39%) of the 96 primary superficial bladder cancers, respectively. No significant association was found between the expression level of p27(Kip1) and tumor stage. Decreased p27(Kip1) staining correlated with higher tumor grade (P = 0.001). Interestingly, a significant association was observed between increased expression of p27(Kip1) and positivity for p53 (>20% positive cells; P < 0.001), A significant correlation was also observed between low expression of p217(Kip1) and decreased disease-free survival (P = 0.0003 by log-rank test) and overall survival (P = 0.01 by log-rank test), Furthermore, on multivariate analysis, low p27(Kip1) protein expression was an independent predictor of reduced disease-free survival (P = 0.018; relative risk = 1.95) second only to tumor stage, These data indicate that p27(Kip1) protein is frequently expressed at low level in poorly differentiated tumors and suggest that this protein might represent a useful prognostic marker for disease recurrence and overall survival in superficial bladder carcinomas.