PD-L1 Expression Is Significantly Associated with Tumor Mutation Burden and Microsatellite Instability Score

Cancers

Deok Geun Kim¹  Yoon-La Choi²  Kyoung-Mee Kim²  Hyunwoo Lee²  Yoon Ah Cho²  Sang Yun Ha²  Hyunjin Kim²  Kee-Taek Jang² 

[1] Department of Clinical Genomic Center, Samsung Medical Center, Seoul 06351, Korea;Samsung Medical Center, Department of Pathology and Translational Genomics, Sungkyunkwan University School of Medicine, Seoul 06351, Korea;

关键词: comprehensive cancer panel assay;    tumor mutation burden;    PD-L1 score;    microsatellite instability;   

DOI  :  10.3390/cancers13184659

来源: DOAJ

【 摘 要 】

Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), microsatellite instability (MSI), and tumor mutation burden (TMB) have been proposed as a predictive biomarker to predict response to immune checkpoint blockade (ICB). We aimed to find the relationship of PD-L1 IHC to TMB and MSI using a comprehensive cancer panel assay (CCPA) with >500 genes in advanced cancer patients. CCPA results from 588 archived tissue samples were analyzed for TMB and MSI. In seven samples, whole exome sequencing confirmed TMB with Pearson’s correlation coefficient of 0.972 and all MSI-high cases were validated by pentaplex PCR. Association of TMB and MSI with their corresponding PD-L1 IHC was analyzed. The median TMB value of 588 cases was 8.25 mutations (mut)/Mb (range 0–426.8) with different distributions among the tumor types, with high proportions of high-TMB (>10mut/Mb) in tumors from melanoma, colorectal, gastric, and biliary tract. The TMB values significantly correlated with PD-L1 expression, and this correlation was prominent in gastric and biliary tract cancers. Moreover, the MSI score, the proportion of unstable MSI sites to total assessed MSI sites, showed a significant correlation with the TMB values and PD-L1 scores. This study demonstrates that PD-L1 expression is significantly associated with TMB and MSI score and this correlation depends on the location of the primary tumor.

【 授权许可】

Unknown