Expression Of PD-L1 And EBV In Gastric Cancer And Its Relationship With Histopathological Characteristics And Prognosis

OBJECTIVES: Tumors positive for Epstein-Barr virus(EBV)were classified as a subtype of gastric cancer(GC)by the Cancer Genome Atlas project.EBV-positive cancers are closely related to over-expression of programmed death-ligand 1(PD-L1)as the immune checkpoint.Here,we evaluated GC for its expression of PD-L1 and EBV with their relationship to patient survival.METHODS: Formalin-fixed paraffin-embedded sections of each patient GC tissue were stained by HE and their histological features were analyzed.Then,sections were stained by immnuohistochemistry for PD-L1 and by RNA in situ hybridization for EBV.We estimated the proportion of Chinese patients with GC who are considered positive for PD-L1 and EBV.Patient survival was evaluated according to PD-L1 and EBV status.RESULT: 14.3%(41/287)of sections showed tumor cell membranous PD-L1 expression and 53.3%(153/287)showed expression within immune cell.Both tumor and immune cell PD-L1 expression were associated with worse tumor invasion and worse overall survival(OS).5.9%(17/287)of sections were EBV positive cases,with a rate of 41.2%(7/17)showing PD-L1 positivity,which was significantly higher than the rate of 12.6%(34/270)in EBV negative.Both tumor and immune stroma PD-L1 expression were associated with worse overall survival(OS).CONCLUSION: PD-L1 was expressed on both tumor cells and immune stroma across all stages,demonstrating that checkpoint inhibition may have activity in early stage as well as late stage disease.Cases with PD-L1 expression were associated with worse clinical stage and OS.EBV infection was associated with higher PD-L1 expression in GC rather than with prognosis,indicating that patients not only with PD-L1 expression but also EBV positive were potential subtypes for immune-basedtherapy in GC.Further study in the GC immune microenvironment may highlight targets for immnue-based therapy.