长单核苷酸重复标记物用于检测微卫星不稳定性的验证。

Validation of Long Mononucleotide Repeat Markers for Detection of Microsatellite Instability.

机构信息

The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

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.

出版信息

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

DOI:10.1016/j.jmoldx.2021.10.011

PMID:34864149

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.

摘要

错配修复缺陷（dMMR）预测实体瘤对免疫检查点抑制剂治疗的反应。长单核苷酸重复（LMR）标志物可能改善微卫星不稳定性（MSI）检测的解读。我们的队列包括错配修复（MMR）功能正常和 dMMR 结直肠癌（CRC）样本、MMR 功能正常和 dMMR 子宫内膜癌（EC）样本、dMMR 前列腺癌样本、其他癌症类型的 MSI-H 样本和各种癌症类型的 MSI-L 样本。MMR 状态通过免疫组织化学染色和/或 MSI 分析系统版本 1.2（V1.2）确定。LMR MSI 面板检测 dMMR 的敏感性和特异性均为 100%在 CRC 中。MSI V1.2 和 LMR MSI 面板在 EC 中的敏感性值分别为 88%和 98%，特异性值均为 100%。LMR 面板在免疫组化检测的 dMMR 前列腺癌中的敏感性为 75%。22 例先前被归类为 MSI-H 的其他癌症类型的样本也使用 LMR MSI 面板被归类为 MSI-H。对于先前被归类为 MSI-L 的 12 个样本，1 个样本使用 LMR MSI 面板被归类为微卫星稳定，8 个为 MSI-L，3 个为 MSI-H。LMR MSI 面板在 CRC 中与 MSI V1.2 面板具有高度一致性，在 EC 中具有更高的敏感性。LMR MSI 面板提高了非结直肠癌的 dMMR 检测能力。