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

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.