Evaluation of microsatellite instability in colorectal adenomas and carcinomas by immunohistochemistry and comparison with histopathological features

Approximately %15 of sporadic colorectal carcinomas (CRCs) develop along the microsatellite instability (MSI) pathway. These tumors have lost the mismatch repair function. Indirect microsatellite instability diagnosis can be made by immunohistochemistry for loss of mismatch repair proteins. A high level of consistency was found between the immunohistochemically detected expression of MLH1 and MSH2 proteins and MSI status determined by molecular means in the CRCs reported in the literature. In this study, MLH1, MSH2, Ki-67 and p53 immunostaining properties with histopathological features of colorectal adenomas and CRCs were evaluated. In this study, a total of 102 cases were selected from the archives of the pathology including 20 tubular adenomas, 20 tubulovillous adenomas, 10 villous adenomas, 25 adenocarcinomas, 10 adenocarcinomas with mucinous component, 14 mucinous adenocarcinomas and 3 signet ring cell carcinomas. The H&E stained slides of the cases were reviewed again and the most suitable paraffin blocks were identified. These tissues were stained for MLH1, MSH2, p53 and Ki-67 primer antibodies in an automated immunohistochemistry slide staining system. Negative staining was observed for MLH1 in 25% and MSH2 in 3.8% of all CRC cases. Compared with adenocarcinoma NOS, (negative staining in 4%) and mucinous adenocarcinomas (negative staining in 50%), mucinous adenocarcinomas showed a higher negative MLH1 staining, which was statistically significant. There was also a statistically significant difference between adenocarcinoma NOS, and signet ring cell carcinomas (negative staining in 66.7%) in terms of negative staining for MLH1. There was no statistically significant difference between adenocarcinoma NOS, and adenocarcinomas with mucinous component (30% and 20% negative staining, respectively) in terms of negative staining for MLH1 and MSH2. There was also no statistically significant difference in MLH1 and MSH2 negative staining between adenocarcinomas with mucinous component and mucinous adenocarcinomas. While 30.8% of MLH1 negative cases were low grade carcinomas, 69.2% were high grade. There was a statistically significant relationship between histological grade and MLH1 negativity. VI There was no statistical significance between MLH1/MSH2 staining and age, gender, tumor localization, p53 staining and histopathological findings such as lymphatic/lymph node invasion, tumor necrosis, and tumor nodule. We found a positive correlation between MLH1 negative staining and intratumoral lymphocytic response and Crohn-like response. 86% of patients with adenomatous polyps were found to be over 50 years of age. An increase in size was detected in polyps that were proportional to the villous features. Villous adenomas were larger than tubulovillous and tubular adenomas, which in turn, tubulovillous adenomas were larger than tubular adenomas. The polyps located in the left colon were larger than those located in the right colon. Polyps with a high degree of dysplasia (mean diameter 1.65 cm) were larger than those with low degree dysplasia (mean diameter 0.76 cm). Villous adenomas had higher dysplasia than tubulovillous adenomas, and tubulovillous adenomas had higher dysplasia than tubular adenomas. A positive correlation was found between the grade of dysplasia and p53 staining intensity and Ki-67 proliferation index. No negative staining was observed for MLH1 and MSH2in any of the tubular, tubulovillous and villous adenomas. In conclusion, no negative staining was evident for MLH1 and MSH2 in tubuler, tubulovillous and villous adenomas with different size, localization and dysplasia. Numerically, mucinous carcinomas and signed ring cell carcinomas showed higher negative staining for MLH1 than adenocarcinoma NOS. There was also a positive correlation between MLH1 negative staining and intratumoral lymphocytic response and Crohn-like response.