Integrated analysis of molecular and clinical prognostic factors in stage II/III colon cancer

Abstract

BackgroundThe prognostic potential of individual clinical and molecular parameters in stage II/III colon cancer has been investigated, but a thorough multivariable assessment of their relative impact is missing.MethodsTumors from patients (N 1404) in the PETACC3 adjuvant chemotherapy trial were examined for BRAF and KRAS mutations, microsatellite instability (MSI), chromosome 18q loss of heterozygosity (18qLOH), and SMAD4 expression. Their importance in predicting relapse-free survival (RFS) and overall survival (OS) was assessed by Kaplan-Meier analyses, Cox regression models, and recursive partitioning trees. All statistical tests were two-sided.Results MSI-high status and SMAD4 focal loss of expression were identified as independent prognostic factors with better RFS (hazard ratio [HR] of recurrence 0.54, 95% CI 0.37 to 0.81, P . 003) and OS (HR of death 0.43, 95% CI 0.27 to 0.70, P . 001) for MSI-high status and worse RFS (HR 1.47, 95% CI 1.19 to 1.81, P