Programmed death-ligand 1 expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+ tumor infiltrating lymphocytes group

Abstract

// Hyeyoon Chang 1 , Woon Yong Jung 2 , Youngran Kang 3 , Hyunjoo Lee 4 , Aeree Kim 1 , Han Kyeom Kim 1 , Bong Kyung Shin 1 , Baek-hui Kim 1 1 Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Guro-gu, Seoul, Republic of Korea 2 Department of Pathology, Catholic Kwandong University International St Mary’s Hospital, Incheon, Republic of Korea 3 Department of Pathology, Green Cross Laboratories, Yongin, Kyeonggi-Do, Republic of Korea 4 Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea Correspondence to: Baek-hui Kim, email: maelstrom@naver.com Keywords: gastric adenocarcinoma, PD-1, PD-L1, CTLA-4, prognosis Received: May 20, 2016      Accepted: October 02, 2016      Published: October 12, 2016 ABSTRACT Gastric adenocarcinoma is one of the most common causes of cancer-related death. In this study, we conducted immunohistochemical studies for PD-L1, PD-1, CTLA-4, and CD8 using tissue microarrays from 464 gastric cancer samples and evaluated the correlations between their expression, clinicopathologic factors, and five-year overall survival. PD-L1 and PD-1 expression was significantly correlated with several adverse prognostic pathologic factors, including higher T-stage, diffuse Lauren histologic type, and lymphatic invasion. Conversely, CTLA-4 expression was correlated with factors of favorable clinical outcomes. A complete case analysis revealed that high PD-L1 and PD-1 expression had an adverse effect on five-year overall survival in univariate analyses. Subgroup analyses wherein patients were divided into two groups according to CD8+ tumor infiltrating lymphocyte levels (high and low) showed that high PD-L1 expression was a significant adverse prognostic factor only in the high CD8+ tumor-infiltrating lymphocytes group. Further research and clinical trials are needed to determine the clinical usefulness of these findings.