Absence of the Cell Cycle Inhibitor p27Kip1 Protein Predicts Poor Outcome in Patients With Stage I-III Colorectal Cancer

Claudio Belluco MD, PhD, Giovanni Esposito MD, Roberta Bertorelle PhD, Annarosa Del Mistro MD, Ambrogio Fassina MD, Giulia Vieceli MD, Luigi Chieco-Bianchi MD, Donato Nitti MD, Mario Lise MD
Original Article
Volume 6, Issue 1 / January ,

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Abstract

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 study explores the prognostic significance of the absence of the p27^Kip1 protein in patients with colorectal cancer (CRC).

Methods: Formalin-fixed tumor sections from 124 patients who underwent curative resection for stage I-III CRC were analyzed by immunohistochemistry using 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 (DFS) and overall survival (OS) were 76% and 85%, respectively, in patients with tumors with p27^Kip1 protein expression and 34% and 40%, respectively, in those whose tumors lacked p27^Kip1 protein expression (P < .001). At multivariate analysis, tumor stage (III vs. I-II) and p27^Kip1 protein status (absence vs. presence) were found to be independent prognostic factors for DFS and OS.

Conclusions: Lack of p27^Kip1 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.

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