Analysis of the relationship of DNA mismatch repair with clinicopathologic features and prognosis of colon cancer

Objective To explore the relationship between DNA mismatch repair (MMR) and clinicopathologic features and prognosis in patients with stages Ⅱ and Ⅲ colon cancers. Methods The clinical and pathological data of 440 patients with stage Ⅱ/Ⅲ colon cancer after radical resection were retrospectively reviewed and analyzed. Immunohistochemical staining was used to assess the expression of MMR proteins (MLH1, MSH2, MSH6 and PMS2), and the correlation between DNA MMR and clinicopathological features and prognosis of colon cancers was analyzed. Results Of the 440 tumor samples tested for DNA mismatch repair status, 90 (20.5%) demonstrated defective DNA mismatch repair and 350 (79.5%) had proficient DNA mismatch repair. Defective DNA mismatch repair (dMMR) was associated with young patients (≤60), proximal colon cancer, stage Ⅱ, poorly differentiated adenocarcinoma and mucinous adenocarcinoma (P<0.05 for all). Among the 440 patients, 126 (28.6%) cases had recurrence or metastasis and 93 (21.1%) died during the median follow-up of 61.0 months. The five-year disease-free survival (DFS) rate was 82.2% among the patients with tumor exhibiting dMMR, significantly higher than that in patients with tumors exhibiting pMMR (68.9%, P=0.02). The univariate and mutlivariate analyses showed that the MMR status is an independent factor affecting 5-year disease-free survival and overall survival(OS) in colon cancer patients (P<0.05 for both). Conclusions Defective DNA mismatch repair (dMMR) is associated with patients with proximal colon cancer, stage Ⅱ and poorly defferentiated adenocarcinoma and mucinous adenocarcinoma. The prognosis for patients with dMMR is better than those with pMMR. dMMR may be a useful biomarker for the prognosis of colon cancer. Key words: Colonic neoplasms; DNA mismatch repair; Prognosis