Poor prognosis in Epstein–Barr virus-negative gastric cancer with lymphoid stroma is associated with immune phenotype

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2018-11, Vol.21 (6), p.925-935
• Main Authors: Cho, Charles J., Kang, Hyo Jeong, Ryu, Yeon-Mi, Park, Young Soo, Jeong, Hui Jeong, Park, Young-Mi, Lim, Hyun, Lee, Jeong Hoon, Song, Ho June, Jung, Hwoon-Yong, Kim, Sang-Yeob, Myung, Seung-Jae
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adult; Aged; Apoptosis; B7-H1 Antigen - metabolism; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Cancer Research; CD3 antigen; CD3 Complex - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - pathology; Cell death; Cell density; Epstein-Barr virus; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - pathology; Epstein-Barr Virus Infections - virology; Female; Gastric cancer; Gastroenterology; Herpesvirus 4, Human - pathogenicity; Humans; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - pathology; Lymphoid Tissue - pathology; Male; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Middle Aged; Oncology; Original Article; PD-1 protein; PD-L1 protein; Phenotypes; Prognosis; Programmed Cell Death 1 Receptor - metabolism; Retrospective Studies; Stomach Neoplasms - immunology; Stomach Neoplasms - mortality; Stomach Neoplasms - surgery; Stomach Neoplasms - virology; Stroma; Surgical Oncology; Survival Analysis; Tumor cells; Tumor Microenvironment - immunology; Tumor-infiltrating lymphocytes
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-018-0820-3

Background Gastric cancer with lymphoid stroma (GCLS) is pathologically characterized by poorly developed tubular structures with a prominent lymphocytic infiltration. Its clinical and prognostic features differ in patients positive and negative for Epstein–Barr virus (EBV) infection. This study analyzed the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and the density of tumor-infiltrating lymphocytes (TILs) including CD3+ and CD8+ T cells, as well as their prognostic significance in patients with GCLS. Methods The study included 58 patients with GCLS (29 EBV+ and 29 EBV−) who underwent curative resection. Expression of CD3, CD8, PD-1, and PD-L1 in tumor cells and TILs was analyzed using a quantitative multispectral imaging system (Opal™), with these results validated by immuno-histochemical assays for PD-L1 on whole slide sections. Results The proportion of tumors overexpressing PD-L1 (31.0 vs. 0%, P  = 0.002), TIL density (4548 vs. 2631/mm 2 , P