The Clinicopathological Features and Genetic Alterations in Epstein–Barr Virus-Associated Gastric Cancer Patients after Curative Surgery

• Published in: Cancers Vol. 12; no. 6; p. 1517
• Main Authors: Fang, Wen-Liang, Chen, Ming-Huang, Huang, Kuo-Hung, Lin, Chien-Hsing, Chao, Yee, Lo, Su-Shun, Li, Anna Fen-Yau, Wu, Chew-Wun, Shyr, Yi-Ming
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 10.06.2020; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Cancer therapies; Drug resistance; Epstein-Barr virus; Gastric cancer; Helicobacter pylori; Immunotherapy; Infections; Intestine; Liver; Medical prognosis; Metastases; Metastasis; Mutation; Patients; PD-L1 protein; Prognosis; Stroma; Studies; Surgery; Survival analysis; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12061517

Background: Epstein–Barr virus (EBV)-associated gastric cancer (GC) is one of four major gastric cancer types and is traditionally considered to be related to lymphoepithelioma-like GC. Few studies have investigated the clinical significance of EBV infection in intestinal/solid type, diffuse (poorly cohesive) type, and lymphoepithelioma-like GC. Methods: A total of 460 GC patients receiving curative surgery were enrolled. The clinicopathological features, genetic alterations and prognoses were compared between patients with and without EBV infection. Results: EBV-positive GC patients (n = 43) had more tumors located in the upper and middle stomach, more common in lymphoepithelioma-like carcinoma, more lymphoid stroma, fewer Helicobacter pylori infections, and higher programmed death-ligand 1 (PD-L1) expression than EBV-negative GC patients. For intestinal/solid type GC, EBV-positive tumors were more likely to be located in the upper and middle stomach, have more lymphoid stroma, fewer Helicobacter pylori infections, higher PD-L1 expression, and more liver metastases than EBV-negative tumors. For diffuse (poorly cohesive) type GC, EBV-positive tumors were more likely to be located in the upper stomach, and have more lymphoid stroma than EBV-negative tumors. For lymphoepithelioma-like GC, EBV-positive tumors had more PI3K/AKT pathway mutations than EBV-negative tumors. Conclusions: Intestinal/solid type GC patients with EBV-positive tumors were associated with higher PD-L1 expression and more liver metastases, while lymphoepithelioma-like GC patients with EBV-positive tumors had more PI3K/AKT pathway mutations. Immunotherapy and targeted therapy may be beneficial for these groups of patients. Routine EBV survey is recommended in GC.