The Significance Of Mismatch Repair Protein Expression And BARF^V600E Mutation In Colorectal Cancer

Objective:To investigate the relationship between the expression of DNA mismatch repair proteins and clinicopathological features in the colorectal cancer(CRC), and analyze the role of screening CRC with deficient mismatch repair and Lynch syndrome by joint detection of BRAFV600 E.Methods:1. Tissue microarray and immunohistochemical staining were used to detect the expression of four mismatch repair proteins in paraffin embedded tissue samples from 980 CRC patients. Absent expression of one or more of these proteins in the tumor cells were classified as the MMR deficient(d MMR), all positive expression were classified as the MMR proficient(p MMR).2. All 108 cases of d MMR CRC were detected BRAFV600 E mutant by using PCR technique, and selected 60 cases of p MMR CRC randomly as a control group.Results:1. Negative staining of MMR proteins was found in 11% cases analyzed. The frequency of loss expression in MLH1, PMS2, MSH2 and MSH6 was 7.3%, 7.1%, 2.0%and 1.9%, respectively. Among them, double proteins absence were found in MLH1/PMS252 cases(5.3%) and in MSH2/MSH6 14 cases(1.4%),and the expression of MLH1 and PMS2, MSH2 and MSH6 showed significant positive correlation(rs=0.712, P<0.001).Three cases had been shown abnormal for 4 MMR proteins.2. Patients with d MMR and p MMR CRC had difference in age, tumor location, tumor size, histological type, lymph node metastasis, clinical stage and Ki-67(P<0.05), but had no obvious difference in gender, gross type, differentiation degree, infiltration depth,vascular invasion, nerve recidivism, distant metastasis and CEA levels(P>0.05).3. Of 108 patients with d MMR, 32.4% harbored BRAFV600 E mutant. However, the incidence of BRAF mutant in 60 cases with p MMR CRC was only 16.7%. The rate of BRAFV600 E mutant in d MMR group was obviously higher than p MMR group(P<0.05).The frequency of BRAFV600 E mutation in patients with a loss of MLH1 or MLH1-PMS2 was higher than that with expression of MLH1,but there was no statistical significance(P>0.05).Conclusion:1. The proportion of d MMR CRC is lower in our country, and MLH1, PMS2 is more common than MSH2 and MSH6.2. There is a close relationship between MMR proteins and the clinicopathological characteristics of colorectal cancer3. The rate of BRAFV600 E mutation in d MMR CRC is higher than p MMR CRC.Combined detection of MMR protein and BRAFV600 E mutation could carry on the preliminary classification of d MMR CRC, simplify the process of Lynch syndrome screening, facilitate the clinical treatment and management.