Interpreting IHC and NGS Testing for MMR and MSI Status

Dr. Redfern provides a detailed, clinically practical overview of mismatch repair and microsatellite instability testing in endometrial cancer, explaining the mechanistic differences between immunohistochemistry—which assesses protein expression of MLH1, PMS2, MSH2, and MSH6—and next-generation sequencing or PCR-based microsatellite instability testing. She addresses the approximately 5% to 10% discordance rate between the two methods and describes her approach of favoring the positive result, ideally with pathologist review of the original immunohistochemistry slides. Dr. Wenham raises the clinical implications of MLH1 promoter hypermethylation as a cause of apparent mismatch repair deficiency, and Dr. Redfern clarifies that these patients should still be classified as mismatch repair–deficient and are expected to benefit from immunotherapy. The panel closes with a reminder that endometrial cancer diagnoses—increasingly occurring in younger patients—warrant germline genetic counseling regardless of mismatch repair status.