The PMS2 antibody is a crucial tool in molecular pathology for assessing DNA mismatch repair (MMR) function. PMS2 encodes a protein component of the MutLα heterodimer, which partners with MLH1 to correct DNA replication errors. Germline mutations in PMS2 are linked to Lynch syndrome, a hereditary cancer predisposition syndrome associated with colorectal, endometrial, and other cancers. Immunohistochemistry (IHC) using PMS2 antibodies helps identify loss of protein expression in tumor tissues, indicating MMR deficiency (dMMR). This deficiency serves as a biomarker for microsatellite instability (MSI), guiding Lynch syndrome diagnosis, prognosis, and therapeutic decisions (e.g., immunotherapy response).
PMS2-specific antibodies are particularly valuable because its expression relies on MLH1 binding. In IHC, concurrent loss of PMS2 and MLH1 often suggests sporadic MLH1 promoter hypermethylation, whereas isolated PMS2 loss may indicate germline mutations. However, antibody specificity challenges arise due to homologous pseudogenes and protein cross-reactivity. Recent advancements in monoclonal antibody design have improved detection accuracy. Clinically, PMS2 IHC is part of a standard MMR panel (with MLH1. MSH2. MSH6) for colorectal and endometrial cancer screening. Its role extends to research on carcinogenesis, MMR mechanisms, and targeted therapies. Proper interpretation requires correlation with genetic testing and clinical history.