Validation of Long Mononucleotide Repeat Markers for Detection of Microsatellite Instability

John H Lin; Suping Chen; Aparna Pallavajjala; Liana B Guedes; Tamara L Lotan; Jeffery W Bacher; James R Eshleman

doi:10.1016/j.jmoldx.2021.10.011

Validation of Long Mononucleotide Repeat Markers for Detection of Microsatellite Instability

J Mol Diagn. 2022 Feb;24(2):144-157. doi: 10.1016/j.jmoldx.2021.10.011. Epub 2021 Dec 2.

Authors

John H Lin¹, Suping Chen¹, Aparna Pallavajjala¹, Liana B Guedes¹, Tamara L Lotan², Jeffery W Bacher³, James R Eshleman⁴

Affiliations

¹ The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
² The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
³ Promega Corp., Madison, Wisconsin.
⁴ The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: jeshlem@jhmi.edu.

PMID: 34864149
DOI: 10.1016/j.jmoldx.2021.10.011

Abstract

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 mismatch repair (MMR) proficient and dMMR colorectal cancer (CRC) samples, MMR proficient and dMMR endometrial cancer (EC) samples, dMMR prostate cancer 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 staining and/or MSI Analysis System Version 1.2 (V1.2). The sensitivity and specificity of the LMR MSI panel for dMMR detection were both 100% in CRC. The sensitivity values of the MSI V1.2 and LMR MSI panels in EC were 88% and 98%, respectively, and the specificity values were both 100%. The sensitivity of the LMR panel was 75% in dMMR prostate cancer detected by immunohistochemistry. 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 microsatellite stable 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 noncolorectal cancers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms* / diagnosis
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / pathology
DNA Mismatch Repair / genetics
Humans
Immunohistochemistry
Male
Microsatellite Instability*
Sensitivity and Specificity