Analysis of DNA Mismatch Repair Proteins Expression and BRAF V600E Mutation in a Subset of Early- and Late-onset Colorectal Carcinoma Patients in Mexico

Abstract

A third of colorectal carcinomas (CRC) affect patients <50 years of age. Fifteen percent of CRC cases with microsatellite instability are due to inherited germ-line mutations in DNA mismatch repair genes. The rest have an epigenetic hypermethylation of the MLH1 promoter in whom the BRAF V600E mutation is a common hallmark. Immunohistochemistry helps to classify colorectal cancers with 100% specificity and 92% sensitivity. We undertook this study to determine if age is a risk factor for defective MMR protein expression and BRAF mutations in our population and to compare these results with the histopathological tumor features. Immunohistochemistry for MLH1 and MSH2 and RT-PCR BRAF V600E mutation was performed on tissue specimens from 57 patients <50 years of age. Data on age, gender, tumor location, histology, depth of infiltration, and the presence of metastatic lymph nodes were collected. Forty eight patients >50 years of age were used as a control group. A statistical analysis using ANOVA, χ(2), and Spearman's rho test were performed. Absent MMR protein expression was more prevalent in patients <50 years of age. No BRAF V600E mutations were detected in either group. Medullary and mucinous types were more prevalent among young patients, whereas intestinal type was more frequent in older patients (p= 0.0008). No differences were found regarding clinicopathological stages between groups. We found an association between young age and defective MMR expression. No V600E BRAF mutations were detected in either group.