Absence of the cell cycle inhibitor p27Kip1 protein predicts poor outcome in patients with stage I-III colorectal cancer.

Abstract

The p27Kip1 protein regulates the G1 to S phase transition of cell cycle by binding to and inhibiting the cyclin E/Cdk2 complex. This study explores the prognostic significance of the absence of the p27Kip1 protein in patients with colorectal cancer (CRC). Formalin-fixed tumor sections from 124 patients who underwent curative resection for stage I-III CRC were analyzed by immunohistochemistry using MoAb anti-p27KiP1. Detectable levels of p27Kip1 protein were found in 86% of tumors. Median follow-up was 55 months. Actuarial 5-year disease-free survival (DFS) and overall survival (OS) were 76% and 85%, respectively, in patients with tumors with p27Kip1 protein expression and 34% and 40%, respectively, in those whose tumors lacked p27Kip1 protein expression (P < .001). At multivariate analysis, tumor stage (III vs. I-II) and p27Kip1 protein status (absence vs. presence) were found to be independent prognostic factors for DFS and OS. Lack of p27KiP1 protein expression in CRC is a negative prognostic marker and may therefore be useful in selecting early-stage patients more likely to benefit from adjuvant treatment.