Validation of Long Mononucleotide Repeat Markers for Detection of Microsatellite Instability

Mismatch repair deficiency (dMMR) predicts response to immune checkpoint inhibitor therapy in solid tumors. Long mononucleotide repeat (LMR) markers may improve the interpretation of microsatellite instability (MSI) assays. Our cohorts included MMR proficient (pMMR) and dMMR colorectal cancer (CRC) samples, pMMR and dMMR endometrial cancer (EC) samples, dMMR prostate cancer (PC) samples, MSI-high (MSI-H) samples of other cancer types and MSI-low (MSI-L) samples of various cancer types. MMR status was determined by immunohistochemical (IHC) staining and/or MSI Analysis System Version 1.2. The sensitivity and specificity of the LMR MSI panel for dMMR detection were both 100% in CRC. The sensitivity of the MSI V1.2 and LMR MSI panels in EC were 88% versus 98%, respectively, and the specificity were both 100%. The sensitivity of the LMR panel was 75% in dMMR PC detected by IHC. The 22 samples of other cancer types that were previously classified as MSI-H were also classified as MSI-H using the LMR MSI panel. For the 12 samples that were previously classified as MSI-L, 1 sample was classified as MSS using the LMR MSI panel, 8 as MSI-L, and 3 as MSI-H. The LMR MSI panel showed high concordance to the MSI V1.2 panel in CRC and greater sensitivity in EC. The LMR MSI panel improves dMMR detection in non-colorectal cancers.