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

摘要

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.