Expression status of MLH1 and MSH2 mismatch repair proteins in colorectal carcinoma

Abstract

Abstract Background Colorectal carcinoma (CRC) is a main cause of morbidity and mortality worldwide. Lynch syndrome or hereditary nonpolyposis colorectal carcinoma is a cancer syndrome that accounts for 5–10% of cases of CRCs, and it is caused by a germline mutation in one or more of mismatch repair (MMR) genes, that is, MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6, PMS1 homolog (PMS2), and epithelial cellular adhesion molecule. Nearly 90% of cases have mutations in either MLH1 or MSH2 gene. Aim To study the immunohistochemistry of MLH1 and MSH2 MMR proteins in CRC and to study the association of abnormal MMR protein expression with clinicopathological parameters. Patients and methods This study included 48 cases of consecutive colectomy specimens submitted to the Pathology Department of Al-Azhar University hospitals and some private laboratories. The patients’ age ranged between 22 and 81 years (median, 53 years), and 35 (72.9%) cases were male and 13 (27.1%) cases were females. Results Among the 48 studied CRC cases, 11 (22.9%) cases were MMR deficient, whereas 37 (77.1%) cases were MMR proficient. MMR defects owing to germline mutations of MSH2 were eight (72.7%) cases of the MMR deficient and that due to the functional missense mutation or hypermethylation of MLH1 were three (27.3%) cases. Conclusions Immunohistochemistry for MLH1 and MSH2 is a rapid, reliable, effective, and relatively inexpensive method to detect MMR deficiency in CRC tumors. The patterns of expression of MMR protein demonstrated distinct associations with right-sided mucinous colon carcinoma and high tumor grade, which may be valuable for prognosis and clinical treatment of CRCs.