Cyclin-dependent kinase inhibitor p27(KIP1) is expressed preferentially inearly stages of urothelial carcinoma

Objectives. To evaluate the expression of p27(KIP1) and p21(CIP1) and the p rognostic values of both markers in urothelial carcinoma. The expression of the cyclin-dependent kinase inhibitor p27(KIP1) characterizes early-stage and well-differentiated carcinomas of the colon, breast, and prostate and i s associated with an improved prognosis. In urothelial carcinoma, its expre ssion has not been as well investigated. Another cyclin-dependent kinase in hibitor, p21(CIP1), is expressed in early-stage bladder tumors, but publish ed data on its prognostic value are contradictory. Methods. Expression of p27(KIP1) and p21(CIP1) was analyzed by immunohistoc hemistry in 114 urothelial carcinoma specimens from 77 patients. The Ki67 i ndex was determined as an indicator of cell proliferation. The expression o f the markers was correlated with tumor recurrence and progression during a n average follow-up period of 3.9 years. Results. Expression of p27(KIP1) was significantly more frequent in superfi cial than in muscle-invasive tumors (chi-square test, P = 0.012; Fisher's e xact test, P = 0.014). Although similar overall, the expression pattern of p27(CIP1) did not match on a tumor-by-tumor basis. No correlation was seen with the Ki67 index. Patients with tumors displaying strong positive staini ng for p27(KIP1) Or p21(CIP1) had fewer recurrences and progression events, but the difference was not statistically significant. Instead, a Ki67 inde x of less than 10% was significantly (P = 0.0335) related to a lack of recu rrence. Conclusions. Neither p27(KIP1) nor P21(CIP1) appear to be good predictors o f tumor progression in urothelial carcinoma, even though their expression i s strongly decreased in muscle-invasive tumors. UROLOGY 56: 689-695, 2000. (C) 2000, Elsevier Science Inc.