Abstract 3954: Evaluation of long mononucleotide repeat markers for detection of microsatellite instability

Abstract Microsatellite instability (MSI) and mismatch repair immunohistochemistry are biomarkers of defective MMR (dMMR) that predict response to immune checkpoint inhibitor therapy in solid tumors. The microsatellites in the Promega MSI Analysis System Version 1.2 may not be ideal to detect MSI in certain cancer types. Long mononucleotide repeat (LMR) markers may improve detection of microsatellite instability in early colorectal lesions and non-colorectal cancers.In this study, we compared the performance of the current gold standard, MSI Analysis System Version 1.2 (Promega), which consists of 5 mononucleotide repeat markers (21-27 bases), with a new LMR kit (Promega), which consists of 4 markers from the MSI V1.2 panel and 4 LMR loci (52-60 bases). We studied five cohorts including 24 MMR proficient (pMMR) and 24 dMMR colorectal cancer (CRC) samples, 24 pMMR and 42 dMMR endometrial cancer (EC) samples, 12 dMMR prostate cancer (PC) samples, 22 MSI-high (MSI-H) samples of other cancer types, and 12 MSI-low (MSI-L) samples, where MMR status was confirmed by immunohistochemical (IHC) staining and/or MSI Analysis System Version 1.2.The specificity and sensitivity of the LMR MSI panel for dMMR detection were both 100% in CRC. The specificity of the MSI V1.2 and LMR MSI panels in EC was both 100%, and the sensitivity was 88% versus 98%, respectively. The 22 MSI-high (MSI-H) samples of other cancer types, these include cholangiocarcinoma, appendix, duodenal, pancreatic and gastric cancer, which were previously classified as MSI-H by using the MSI V1.2 panel were also classified as MSI-H by using the LMR MSI panel. Among 12 samples that were previously classified as MSI-L by the MSI V1.2 panel, 9 of the samples were classified as MSI-L, and 3 of the samples were diagnosed as MSI-H using the MSI LMR panel. The LMR panel has performed well on 80 samples over the past 6 months.The LMR MSI panel is highly concordant with the MSI V1.2 panel for dMMR detection in colorectal cancer and showed increased sensitivity in endometrial cancer. The LMR MSI panel showed improved dMMR detection in non-colorectal cancers. Citation Format: Suping Chen, John H. Lin, Aparna Pallavajjala, Tamara L. Lotan, Jeffery W. Bacher, James R. Eshleman. Evaluation of long mononucleotide repeat markers for detection of microsatellite instability. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3954.