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

Abstract

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.