Prognostic value and expression of p21(waf1/cip1) protein in prostate cancer

BACKGROUND p21(waf1/cip1) protein is a cyclin‐dependent kinase inhibitor able to arrest the cell cycle at the G1 phase by inhibiting DNA replication. The expression of p21(waf1/cip1) and its prognostic value in prostate cancer are largely unexplored. METHODS We used immunohistochemistry to analyze the expression of p21(waf1/cip1) in 213 prostate cancer cases, and the results were related to other known prognostic factors and patient survival during a long‐term follow‐up. RESULTS The expression of p21 (waf1/cip1) protein was significantly associated with high Gleason score (P = 0.001), DNA aneuploidy (P = 0.013), high S‐phase fraction (P = 0.019), and expression of Ki‐67 (P = 0.021) and bcl‐2 (P = 0.001) as well as cyclin A (P = 0.035) and D proteins (P < 0.001). In univariate survival analysis the signal of p21(waf1/cip1) was significantly related to unfavorable prognosis (P = 0.010) both in the entire cohort and in local tumors (P = 0.034). In multivariate analysis, M‐category, clinical T‐category, Gleason score, and patient age were independent prognostic factors. In local tumors the expression of p21(waf1/cip1) together with clinical T‐category and S‐phase fraction were significant independent predictors of cancer related survival. CONCLUSIONS The results suggest that the expression of p21(waf1/cip1) protein is associated both with cell proliferation and patient survival in prostate cancer. Prostate 39:8–15, 1999. © 1999 Wiley‐Liss, Inc.