Absence of hMLH1 or hMSH2 Expression as a Stage-Dependent Prognostic Factor in Sporadic Colorectal Cancers

Abstract

Background. The predictive role of mismatch repair (MMR) status for survival after sporadic colorectal cancer remains a point of controversy. This study was designed to test the prognostic value of MMR status in sporadic colorectal cancers. Methods. The study included 318 patients with sporadic colorectal cancer who underwent primary tumor resection. MMR status was determined by the immunohistochemical analysis of hMLH1 and hMSH2 expression. Results. Thirty-six carcinomas (11.3%) showed abnormal MMR protein expression (22 hMLH1 negative and 14 hMSH2 negative) and were classified as MMR-defective tumors. An MMR defect was strongly associated with a reduced likelihood of lymph node (odds ratio, 0.32; 95% confidence interval [95% CI], 0.13-0.75) or distant organ metastases at diagnosis (odds ratio, 0.07; 95% CI. 0.01-0.62), independent of the clinicopathological features. Overall survival was significantly better in patients with MMR-defective tumors than in those with MMR-intact tumors (P = 0.013). In the subgroup analysis by stage, adjusted for other potential confounding variables. MMR status was not a statistically significant prognostic factor in stage I and II patients, while the MMR defect predicted a significantly better overall survival in stage 111 and IV patients (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.97; P = 0.045). Conclusions. At initial diagnosis, metastases were found at lower rates in MMR-defective tumors. MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.