Expression of four mismatch repair proteins in colorectal cancer and their application in immunodiagnosis

WANG Ling; CHEN Weiwei; YIN Zongnan

doi:10.3969/j.issn.1007-8096.2025.10.022

Abstract：Objective To investigate the expression patterns of four mismatch repair(MMR)proteins(MLH1,MSH2,MSH6,PMS2)in colorectal cancer(CRC),analyze their correlation with clinicopathological parameters,and evaluate the application value of immunohistochemistry(IHC)in detecting deficient mismatch repair(dMMR)status.Methods Ninety-six CRC cases diagnosed in our hospital from May 2021 to May 2025 were collected.IHC was used to assess the expression of the four MMR proteins.The relationship between MMR status and clinicopathological features was statistically analyzed,and representative histologic and IHC images were evaluated.Results Among the 96 cases,21 cases(21.9%)were detected with dMMR,with concurrent loss of MLH1 and PMS2 being the most common pattern(57.1%).The dMMR status was significantly associated with right-sided colon tumors(P=0.000)and mucinous adenocarcinoma(P=0.011).Although more cases with dMMR were observed in patients aged≤50 years,the difference was not statistically significant(P=0.118).IHC images of cases with dMMR showed loss of nuclear expression in tumor cells,while the surrounding control tissues exhibited clear positive staining,indicating that the interpretation of staining results was accurate and reliable.Conclusion IHC-based detection of the four MMR proteins can effectively identify the dMMR status in CRC,and it is particularly indicative for CRC cases occurring in the right-sided tumors and mucinous adenocarcinoma.This method is rapid,cost-effective,and stable,and it is recommended to be routinely applied in clinical practice for screening dMMR status in CRC and identifying high-risk populations of Lynch syndrome.