Abstract 4215: Comprehensive investigation of programmed death receptor ligand 1 (PD-L1) expression and associated molecular features in gastric cancer patients
Authors: Xiaoqiao Liu, Jeeyun Lee, Kyoung-Mee Kim, Seung Tae Kim, Se Hoon Park, Won Ki Kang, Razvan Cristescu, Senaka Peter
Journal: Cancer Research (2018)

Abstract Purpose We explored PD-L1 expression and analyzed its association with molecular subtypes, clinical features and other molecular markers in Korean gastric cancer (GC) patients. Experimental design As with the Asian Cancer Research Group (ACRG) GC cohort, 300 primary tumor specimens were procured from Samsung Medical Center. Tumor PD-L1 expression was measured by immunohistochemistry (IHC) using the 22C3 PD-L1 antibody pharmDx (Dako) kit. PD-L1 positivity was defined as CPS ≥1%, where CPS is PD-L1+ cells (tumor cells, macrophages, lymphocytes) over the total number of tumor cells, expressed as a percentage. ACRG and The Cancer Genome Atlas (TCGA) molecular subtypes, and other molecular and clinical features including PD-L1 mRNA expression by microarray, tumor mutation burden (TMB) by targeted sequencing, microsatellite instability (MSI) status by IHC, Epstein-Barr virus (EBV) infection by in situ hybridization, Helicobacter pylori (H. pylori) infection by microscope, ERBB2 (HER2) and EGFR overexpression by IHC, signet ring cell and Lauren classification were provided as part of the ACRG collaboration. Spearman correlation test, Wilcoxon rank-sum test, Kruskal-Wallis test were utilized to test the association with PD-L1 expression, and survival was analyzed by Kaplan-Meier method and log-rank test. Results The median age was 64 years (range, 24-86), 101 (34%) were female, and 127 (42%) had stage I/II disease. Prevalence of PD-L1 positivity was 59.3%, with significantly higher expression in stage I samples (P = 0.002). PD-L1 positivity was associated with good prognosis (P = 0.008) especially for early stage (I/II) subjects (N = 127, P = 0.007). PD-L1 mRNA was moderately correlated with protein expression (R = 0.430, P &amp;lt; 0.001). For molecular subtype, PD-L1 expression was associated with ACRG subtype (P &amp;lt; 0.001) with significantly higher expression in MSI subtype (P &amp;lt; 0.001). And for TCGA subtype, the association with PD-L1 expression also existed (N = 238, P &amp;lt; 0.001) with significantly higher expression in MSI and EBV subtype (P &amp;lt; 0.001). H. pylori infection was also associated with higher PD-L1 expression (N = 127, P = 0.001). Signet ring cell carcinoma had significantly lower PD-L1 expression (P &amp;lt; 0.001). PD-L1 expression was also significantly higher in ARID1A or PIK3CA mutant samples (N = 233, FDR adjusted P = 0.038). TMB was found to be weakly correlated with PD-L1 expression (N = 233, R = 0.266, P &amp;lt; 0.001). No significant association was observed between PD-L1 expression and overexpression of ERBB2 or EGFR. Conclusion Our study provides evidence that several molecular features, especially MSI and EBV infection, are significantly associated with higher PD-L1 protein expression, which suggests that PD-L1 IHC may be an appropriate biomarker to screen GC patients for immune checkpoint inhibitors. Citation Format: Xiaoqiao Liu, Jeeyun Lee, Kyoung-Mee Kim, Seung Tae Kim, Se Hoon Park, Won Ki Kang, Razvan Cristescu, Senaka Peter. Comprehensive investigation of programmed death receptor ligand 1 (PD-L1) expression and associated molecular features in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4215.