Clinicopathological features of PD-L1 protein expression, EBV positivity, and MSI status in patients with advanced gastric and esophagogastric junction adenocarcinoma in Japan

Cancer Biol Ther. 2022 Dec 31;23(1):191-200. doi: 10.1080/15384047.2022.2038002.


This real-world study examined the prevalence of programmed death ligand-1 (PD-L1) expression and assessed the frequency of microsatellite instability-high (MSI-H) status and Epstein-Barr virus (EBV) positivity in Japanese patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. This multicenter (5 sites), retrospective, observational study (November 2018-March 2019) evaluated Japanese patients with advanced gastric and GEJ adenocarcinoma after surgical resection (Stage II/III at initial diagnosis) or unresectable advanced cancer (Stage IV). The primary objectives were prevalence of PD-L1 expression (combined positive score [CPS] ≥1), MSI status, and EBV positivity. Tumor specimens of 389/391 patients were analyzed (male, 67.1%; mean age, 67.6 ± 12.2 years); 241/389 (62%) were PD-L1 positive, 24/379 (6.3%) had MSI-H tumors, and 13/389 (3.3%) were EBV positive. PD-L1 expression was higher in tumor-infiltrating immune cells than in tumor cells for lower CPS cutoffs. Among patients with MSI-H tumors and EBV-positive tumors, 19/24 (79.2%) and 9/13 (69.2%), respectively, were PD-L1 positive. A greater proportion of patients with MSI-H tumors (83.3% [20/24]) were PD-L1 positive than those with MSI-low/stable tumors (60.8% [216/355]; p = .0297); similarly, an association was observed between history of H pylori infection and PD-L1 expression. A higher proportion of patients with MSI-H tumors demonstrated PD-L1 expression with a CPS ≥10 (66.7% [16/24]) vs those with MSI-low/stable tumors (24.8% [88/355]; p < .0001). The prevalence of PD-L1 positivity among Japanese patients was comparable to that in previous pembrolizumab clinical trials and studies in gastric cancer. Particularly, higher PD-L1 expression was observed in MSI-H tumors.

Keywords: Adenocarcinoma; Japan; PD-L1; microsatellite instability; stomach.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / pathology
  • Aged
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / genetics
  • Esophageal Neoplasms
  • Esophagogastric Junction / pathology
  • Herpesvirus 4, Human / genetics
  • Humans
  • Japan / epidemiology
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Retrospective Studies
  • Stomach Neoplasms* / metabolism


  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human

Supplementary concepts

  • Adenocarcinoma Of Esophagus

Grant support

This study was funded by MSD K. K., Tokyo, Japan.