Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein–Barr virus status, and cancer genome alterations in metastatic gastric cancer

Akihito Kawazoe, Kohei Shitara, Yasutoshi Kuboki, Hideaki Bando, Takashi Kojima, Takayuki Yoshino, Atsushi Ohtsu, Atsushi Ochiai, Yosuke Togashi, Hiroyoshi Nishikawa, Toshihiko Doi, Takeshi Kuwata

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Background: Recently, the U.S. Food and Drug Administration approved pembrolizumab for patients (pts) with PD-L1-positive metastatic gastric cancer (MGC) based on 22C3 immunohistochemistry (IHC) assay. However, little is known about detailed clinicopathological features of 22C3 PD-L1 expression in MGC. Patients and methods: Pts with histologically confirmed MGC were eligible for this prospective observational study. PD-L1 expression (22C3) on tumor cell (TC) or immune cell (IC) and mismatch repair (MMR) were analyzed by IHC. Epstein–Barr virus (EBV) was detected by in situ hybridization. The expressions of tyrosine kinase receptors (RTKs) and cancer genome alterations were evaluated by IHC or next-generation sequencing. Results: A total of 225 pts were analyzed in this study. PD-L1 expression on TC, PD-L1 on IC, MMR-deficient (D-MMR), and EBV positivity were identified in 8.4, 65.3, 6.2, and 6.2% cases, respectively. PD-L1 expression in TC was more frequently observed in pts with D-MMR (P < 0.001), PIK3CA mutation (P = 0.020), and KRAS mutation (P = 0.002), and PD-L1 on IC was associated with EBV positivity (P = 0.034), and lymph-node metastasis (P < 0.001). PD-L1 expression on either IC or TC was less frequently observed in pts with peritoneal metastasis and Borrmann Type 4. A significant association was not observed between PD-L1 expression and RTKs expression or presence of other gene alterations. PD-L1 expression on either TC or IC was not prognostic factor. Conclusions: 22C3 PD-L1 expression in MGC was associated with distinct clinicopathological features, but was not a prognostic factor.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalGastric Cancer
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 22 2019
Externally publishedYes

Keywords

  • 22C3 PD-L1 expression
  • Cancer genome alterations
  • Epstein–Barr virus
  • Metastatic gastric cancer
  • Mismatch repair

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

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