Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein–Barr virus status in a large cohort of gastric cancer patients

  • Akihito Kawazoe
  • Takeshi Kuwata
  • Yasutoshi Kuboki
  • Kohei Shitara
  • Akiko Kawano Nagatsuma
  • Masaaki Aizawa
  • Takayuki Yoshino
  • Toshihiko Doi
  • Atsushi Ohtsu
  • Atsushi Ochiai
Original Article

DOI: 10.1007/s10120-016-0631-3

Cite this article as:
Kawazoe, A., Kuwata, T., Kuboki, Y. et al. Gastric Cancer (2016). doi:10.1007/s10120-016-0631-3

Abstract

Background

Antibodies against programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) have recently demonstrated promising results in gastric cancer (GC). PD-L1 expression, the presence of tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) deficiency have been proposed as predictive biomarkers for anti-PD-1/PD-L1 antibodies. The aim of this study was to investigate the clinical relevance of PD-L1 expression with TIL, MMR, and Epstein–Barr virus (EBV) status in GC.

Methods

We performed a tissue microarray analysis in 487 advanced GC patients who underwent gastrectomy. PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (TIICs), the densities of TILs, and MMR status were evaluated by immunohistochemistry. EBV was detected by in situ hybridization.

Results

PD-L1 expression on TCs and TIICs, MMR deficiency, and EBV positivity were identified in 22.8, 61.4, 5.1, and 5.1 % cases respectively. PD-L1 expression was more frequently observed in the elderly (TCs P = 0.002), in males (TCs P = 0.029; TIICs P = 0.043), in patients with poorly differentiated adenocarcinoma with solid-type histological features (TCs P < 0.001; TIICs P < 0.001), in patients with MMR deficiency (TCs P < 0.001; TIICs P < 0.001), and in patients with EBV positivity (TCs P = 0.001; TIICs P = 0.050). Strong association was observed between PD-L1 expression and high densities of CD3-positive, CD8-positive, or forkhead box P3 positive TILs (TCs P < 0.001; TIICs P < 0.001). Neither PD-L1 expression on TCs nor that on TIICs was an independent prognostic factor in multivariate analysis.

Conclusions

In GC, PD-L1 expression was associated with distinct clinicopathological features, including high densities of TILs, MMR deficiency, and EBV positivity, but was not a prognostic factor.

Keywords

Gastric cancer Programmed death ligand 1 Tumor-infiltrating lymphocytes Mismatch repair status Epstein–Barr virus 

Supplementary material

10120_2016_631_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (DOCX 42 kb)

Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2016

Authors and Affiliations

  • Akihito Kawazoe
    • 1
    • 2
    • 3
  • Takeshi Kuwata
    • 1
    • 5
  • Yasutoshi Kuboki
    • 2
  • Kohei Shitara
    • 2
  • Akiko Kawano Nagatsuma
    • 1
  • Masaaki Aizawa
    • 4
  • Takayuki Yoshino
    • 2
  • Toshihiko Doi
    • 2
  • Atsushi Ohtsu
    • 2
    • 3
  • Atsushi Ochiai
    • 1
  1. 1.Division of Pathology, Research Cancer for Innovative OncologyNational Cancer Center Hospital EastKashiwaJapan
  2. 2.Department of Gastroenterology and Gastrointestinal OncologyNational Cancer Center Hospital EastKashiwaJapan
  3. 3.Juntendo University Graduate School of MedicineTokyoJapan
  4. 4.Department of SurgeryNiigata Cancer Center Hospital, NiigataNiigataJapan
  5. 5.Department of Pathology and Clinical LaboratoriesNational Cancer Center Hospital EastKashiwaJapan