Absence of the cell cycle inhibitor p27(Kip1) protein predicts poor outcome in patients with stage I-III colorectal cancer

Background: The p27(Kip1) protein regulates the G1 to S phase transition of cell cycle by binding to and inhibiting the cyclin E/Cdk2 complex. This st udy explores the prognostic significance of the absence of the p27(Kip1) pr otein in patients with colorectal cancer (CRC). Methods: Formalin-fixed tumor sections from 124 patients who underwent cura tive resection for stage I-III CRC were analyzed by immunohistochemistry us ing MoAb anti-p27(Kip1). Results: Detectable levels of p27(Kip1) protein were found in 86% of tumors . Median follow-up was 55 months. Actuarial 5-year disease-free survival (D FS) and overall survival (OS) were 76% and 85%, respectively, in patients w ith tumors with p27(Kip1) protein expression and 34% and 40%, respectively, in those whose tumors lacked p27(Kip1) protein expression (P <.001). At mu ltivariate analysis, tumor stage (III vs. I-II) and p27(Kip1) protein statu s (absence vs, presence) were found to be independent prognostic factors fo r DFS and OS. Conclusions: Lack of p27(Kip1) protein expression in CRC is a negative prog nostic marker and may therefore be useful in selecting early-stage patients more likely to benefit from adjuvant treatment.