Deficient mismatch repair and RAS mutation in colorectal carcinoma patients: a retrospective study in Eastern China

Abstract

Objectives To investigate the frequency and prognostic role of deficient mismatch repair (dMMR) and RAS mutation in Chinese patients with colorectal carcinoma. Methods Clinical and pathological information from 813 patients were reviewed and recorded. Expression of mismatch repair proteins was tested by immunohistochemistry. Mutation analyses for RAS gene were performed by real-time polymerase chain reaction. Correlations of mismatch repair status and RAS mutation status with clinicopathological characteristics and disease survival were determined. Results The overall percentage of dMMR was 15.18% (121/797). The proportion of dMMR was higher in patients <50 years old (p < 0.001) and in the right side of the colon (p < 0.001). Deficient mismatch repair was also associated with mucinous production (p < 0.001), poor differentiation (p < 0.001), early tumor stage (p < 0.05) and bowel wall invasion (p < 0.05). The overall RAS mutation rate was 45.88%, including 42.56% (346/813) KRAS mutation and 3.69% (30/813) NRAS mutation (including three patients with mutations in both). KRAS mutation was significantly associated with mucinous production (p < 0.05), tumor stage (p < 0.05) and was higher in non-smokers (p < 0.05) and patients with a family history of colorectal carcinoma (p < 0.05). Overall, 44.63% (54/121) dMMR tumors harbored KRAS mutation, however, dMMR tumors were less likely to have NRAS mutation. Moreover, dMMR, KRAS and NRAS mutation were not prognostic factors for stage I–III colorectal carcinoma. Conclusions This study confirms that the status of molecular markers involving mismatch repair status and RAS mutation reflects the specific clinicopathological characteristics of colorectal carcinoma.

Keywords

• KRAS mutation
• Deficient mismatch repair (dMMR )
• NRAS mutation
• Prognosis
• Clinicopathological characteristics
• Colorectal carcinoma