Microsatellite instability screening in colorectal carcinoma: immunohistochemical analysis of MMR proteins in correlation with clinicopathological features and Ki-67 protein expression

Abstract

Abstract Background Defects in mismatch repair (MMR) system or microsatellite instability (MSI) and detected in colorectal carcinoma (CRC), both in sporadic and more frequently in hereditary cases. Immunohistochemistry (IHC) is the most frequent method for MMR protein deficiency screening in CRCs. In this study, we aimed to evaluate immunohistochemical expression of MMR and Ki-67 in colorectal carcinoma with clinicopathological features. Methods In this study, we evaluated the immunohistochemical expression of MMR proteins including MSH6, MSH2, PMS2 and MLH1 in 50 resection materials with colorectal carcinoma. Their expression is correlated with clinicopathological features of patients together, with Ki-67 protein expression in attempt to screen the most significant predictor of microsatellite instability. Results Of the 50 cases of cancer colon, 28% were classified as MSI-H, 20% were MSI-L, and 52% were MSS. The most frequent pattern in MSI-H tumors was concurrent loss of MSH6 and PMS2 proteins. There was a significant correlation between MMR protein expression pattern with tumor size, grade, T-classification and stage (0.015, 0.0515, 0.0162 and 0.0391), respectively. MSI-H tumors were located more frequently in right colon, early TNM stage and poorly differentiated and infrequent distant metastases. There was a significant correlation between Ki-67 high expression and MSI status patterns in their common biological aspects distinct from MSI-negative tumors. Conclusions Mismatch repair defective colorectal carcinoma has characteristics clinicopathological features different from MSS tumors. The role of immunohistochemistry (IHC) for MSI evaluation is the easiest and effective way for evaluation of MMR deficiency in colorectal carcinoma.

Keywords

• Colorectal carcinoma
• Mismatch repair
• Microsatellite instability-Ki-67