Microsatellite instability and protein expression of MLH1 and MSH2 genes in young Mexican patients less than 50 years of age diagnosed with colorectal cancer.

Diagnosis of colorectal cancer in patients under 45 years old should alert us to possible hereditary forms of this neoplasia. Most cases of hereditary colorectal cancer correspond to Lynch syndrome which is caused by mutations in DNA mismatch repair genes, particularly MLH1 and MSH2. The dysfunction is associated with microsatellite instability which occurs in 95% cases of this syndrome and in 15% of sporadic colorectal cancer. In sporadic colon tumors, downregulation of MLH1 is observed in cases with the BRAF V600E variant, which induces hypermetylation of the MLH1 promoter. Mutation screening for hereditary cancer has impacted the diagnosis, genetic counseling, and early tumor detection in families affected by hereditary colorectal cancer syndromes but mutation screening technologies are seldom available in public health care centers in developing countries. This study aimed to describe immunohistochemistry and microsatellite instability abnormalities in tumor samples archived in a public hospital in Mexico. Paraffin-embedded samples of patients with colorectal cancer, diagnosed at under 50 years old, were studied to analyze correlations among clinical variables, MLH1 and MSH2 protein expression (immunohistochemistry), microsatellite instability (fluorescent PCR-based assay), and BRAF V600E variant (real time PCR). Forty-seven tumor specimens from patients with TNM stage II and above were analyzed. Tumors were mainly located in the proximal colon segment and displayed histologic intestinal variety and infiltration to serosa. Twenty samples showed decreased expression of mismatch repair proteins and 10 of these presented microsatellite instability (7 high and 3 low instability patterns, respectively). There were no instances of BRAF V600E mutation found. Altered MLH1 or MSH2 expression was found in 42.5% of the samples and microsatellite instability was observed in 21.3% of the tumors. These results suggested that about a fifth of the patients were candidates for family assessment and genetic counseling. IJCEP