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

Moore, Assaf; Hikri, Elad; Goshen-Lago, Tal; Barkan, Tamar; Morgenstern, Sara; Brook, Elena; Maderer, Annett; Roth, Wilfried; Gordon, Noa; Kashtan, Hanoch; Brenner, Baruch; Moehler, Markus; Aharon, Irit Ben

<bold>Objective: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusion: </bold>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.

EPSTEIN-Barr virus; STOMACH cancer; ONCOGENIC viruses; EPIDERMAL growth factor receptors

BMC Cancer, 2020, Vol 20, Issue 1, p1

1471-2407

Academic Journal

10.1186/s12885-020-6517-0