Concordance Analysis of Microsatellite Instability via NGS and Mismatch Repair Deficiency via IHC in Endometrial and Colorectal Cancer

Microsatellite instability and mismatch repair deficiency are important biomarkers in colorectal and endometrial cancers, helping guide diagnosis, prognosis, and treatment decisions, particularly for immunotherapy. Mismatch repair status is commonly assessed using immunohistochemistry, while microsatellite instability can be detected through sequencing-based methods. In this study, we analyzed 520 tumor samples from patients with colorectal or endometrial cancer using both approaches to compare their performance. Overall, there was high agreement between the two methods, especially in colorectal cancer. However, in endometrial cancer, a lower level of concordance was observed, with several cases showing mismatch repair deficiency without detectable microsatellite instability. These differences were often explained by specific genetic features, such as mutations in DNA polymerase genes, isolated loss of mismatch repair proteins, or epigenetic alterations. We also found that adjusting the threshold used to define microsatellite instability improved detection accuracy in endometrial tumors. These findings suggest that sequencing-based detection of microsatellite instability is a reliable method but may require tumor-specific optimization. Tailoring thresholds based on cancer type could improve identification of patients who are likely to benefit from immunotherapy and enhance precision in clinical decision-making.