Young-onset gastric cancer and Epstein–Barr Virus (EBV) – a major player in the pathogenesis?

Abstract

Objective: Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC. Methods: Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records. Results: Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort [0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002). Conclusion: Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.

PD-L1 Expression Associated with Epstein—Barr Virus Status and Patients’ Survival in a Large Cohort of Gastric Cancer Patients in Northern Brazil

“…Our findings are also corroborated by the study by Moore et al [41], who found that the subtype of GC EBV-positive is indicative of a good prognosis and is more prevalent in young patients, as in the present study, where the number of young patients is statistically higher than patients older than 64 years of age (p < 0.0001). Another study with a large number of samples (n = 3241) also found results similar to our findings, EBV-positive patients (5%) were young and male, with GC samples histologically poorly differentiated, and patients having a good prognosis when expressing the PD-L1 protein [38].…”

Gastrointestinal Adenocarcinoma Incidence and Survival Trends in South Australia, 1990–2017

“…The evidence in the literature regarding the role of sex in young-onset gastrointestinal adenocarcinoma has been mixed, with some studies reporting a greater incidence rate in males for oesophageal, stomach, and colon and rectal cancers [ 32 , 33 , 34 ], while others reporting females showing greater incidence rates for colon cancer [ 35 ]. This study has demonstrated that the incidence of young-onset gastrointestinal adenocarcinomas has significantly increased in males and females between the ages of 18 and 50 years, with the increase being more pronounced in males.…”

Clinicopathological and Immunomicroenvironment Characteristics of Epstein–Barr Virus-Associated Gastric Cancer in a Chinese Population

“…The cases in the present study were derived from more than 1,328 samples, which is the largest number of cases reported thus far for the overall analysis of the immune microenvironment. A study involving Americans reported the greater prevalence of the EBV subtype in young-onset GC, which might play a key role in the pathogenesis ( 17 ). A Japanese study found that an age <65 years was an independent risk factor for lymph node metastasis in patients with EBVaGC ( 18 ).…”