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

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2017-05, Vol.20 (3), p.407-415
• Main Authors: Kawazoe, Akihito, Kuwata, Takeshi, Kuboki, Yasutoshi, Shitara, Kohei, Nagatsuma, Akiko Kawano, Aizawa, Masaaki, Yoshino, Takayuki, Doi, Toshihiko, Ohtsu, Atsushi, Ochiai, Atsushi
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adult; Aged; Aged, 80 and over; B7-H1 Antigen - metabolism; Cancer Research; Cohort Studies; DNA Mismatch Repair - genetics; Epstein-Barr virus; Female; Gastric cancer; Gastroenterology; Herpesvirus 4, Human - pathogenicity; Humans; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Stomach Neoplasms - virology; Surgical Oncology; Survival Analysis; Tissue Array Analysis
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-016-0631-3

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