Genetic and immunohistochemical detection of microsatellite instability in colorectal adenocarcinoma and precancerous lesions

Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract. It is known that the vast majority of CRC in the colon resulting from the previously found adenoma. In inflammatory bowel diseases (IBD) in particular after long periods the risk of CRC increases. In colorectal carcinogenesis tumors with Microsatellite Instability(MSI) shows a better prognosis. So it is important to show MSI in CRC. This study aimed to determine microsatellite unstable cases which have a better prognosis and better response to treatment, in CRC, adenomatous polyps and IBD. In our study, 40 CRC, 40 adenomatous polyps and 40 IBD diagnosed consecutive patients of total 120 patients with no specific features, were included. Immunohistochemical MLH1 and MLH2 antibodies were applied to all patients. Also in all cases MSI status was assessed by Polymerase Chain Reaction (PCR) and sequence analysis from the isolated DNA samples using primers Bethesda panel. 20% of cases showed absent MLH1 expression and 12,5% of cases showed absent MSH2 expression. 10,8% of cases showed MSI by PCR. Either immunohistochemical loss of expression or presence of mutation was the highest in adenocarcinoma group and the lowest in IBD group. In comparison of MLH1 and MSH2 immunohistochemical stains, positive correlation were found for all groups between two markers staining distribution (p=0,003). A statistically significant difference was found between MSI rates among the patients with adenocarcinoma and IBD groups (p=0,046). Differences between adenocarcinoma and adenomatous polyps groups were not significant (p=0,07). Significant positive correlation was observed between MSI and immunohistochemically loss of MLH1 and MSH2 expression (p=0,01, p=0,49). In our study, the loss of MLH1 and MSH2 expression, which performed by immunohistochemical methods, correlated positively with genetically determined MSI in all groups. Thus, instead of PCR which is a slow and expensive method, a cheaper and practical method, immunohistochemistry can be applied especially in selected patients was reached as a result. The results of our study are noteworthy because of these patients have better prognosis and a better ability to respond the treatment. Key words: CRC, Adenomatous Polyps, IBD, MLH1, MSH2, Microsatellite Instability, Immunohistochemistry, PCR.