Cyclin-dependent kinase inhibitor p27KIP1 is expressed preferentially in early stages of urothelial carcinoma

Objectives. To evaluate the expression of p27(KIP1) and p21(CIP1) and the prognostic 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 is associated with an improved prognosis. In urothelial carcinoma, its expression has not been as well investigated. Another cyclin-dependent kinase inhibitor, p21(CIP1), is expressed in early-stage bladder tumors, but published data on its prognostic value are contradictory. Methods. Expression of p27(KIP1) and p21(CIP1) was analyzed by immunohistochemistry in 114 urothelial carcinoma specimens from 77 patients. The Ki67 index was determined as an indicator of cell proliferation. The expression of the markers was correlated with tumor recurrence and progression during an average follow-up period of 3.9 years. Results. Expression of p27(KIP1) was significantly more frequent in superficial than in muscle-invasive tumors (chi-square test, P = 0.012; Fisher's exact 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 staining for p27(KIP1) Or p21(CIP1) had fewer recurrences and progression events, but the difference was not statistically significant. Instead, a Ki67 index of less than 10% was significantly (P = 0.0335) related to a lack of recurrence. Conclusions. Neither p27(KIP1) nor P21(CIP1) appear to be good predictors of tumor progression in urothelial carcinoma, even though their expression is strongly decreased in muscle-invasive tumors. UROLOGY 56: 689-695, 2000. (C) 2000, Elsevier Science Inc.