Prognostic Significance of p27kip-1 Expression in Colorectal Adenocarcinomas Is Associated with Tumor Stage

Abstract

Purpose: Although the decreased expression of p27kip-1, a cyclin-dependent kinase inhibitor, has been correlated with advanced tumor stage and short survival of patients with colorectal adenocarcinomas (CRCs), its prognostic value based on the tumor site, tumor stage, and patient ethnicity was not assessed. Therefore, in this study, we investigated whether the prognostic value of p27kip-1 expression varies with the tumor site, tumor stage and patient ethnicity. Experimental Design: We evaluated 206 (85 African Americans and 121 Caucasians) archival tissue specimens of first primary CRCs for immunohistochemical expression of p27kip-1, and its prognostic significance was analyzed using univariate Kaplan-Meier and multivariate Cox regression survival methods. Results: Although, similar proportion of CRCs with decreased p27kip-1 expression was observed in all stages (range, 26-36%), the decreased p27kip-1 expression has been shown as a marker of poor prognosis only for patients with stage III tumors both in univariate (log-rank test, P = 0.014) and multivariate (hazard ratio = 3.2, 95% confidence interval = 1.3-7.7; P = 0.01) survival analyses. The decreased expression of p27kip-1 was associated with a high histologic grade (P = 0.016) in stage II CRCs, and with distal tumors (P = 0.001), tumor invasion (P = 0.044), and with local recurrence (P = 0.008) in stage III CRCs. Conclusions: No prognostic significance was found for p27 kip-1 expression in stages I, II, or IV CRCs, and its prognostic value was not associated with either ethnicity or tumor location. These studies suggest that decreased expression of p27kip-1 is an indicator of poor prognosis and aids in identifying a subset of patients with aggressive forms of stage III CRCs.