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

Authors
  • Moore, Assaf1, 2
  • Hikri, Elad2
  • Goshen-Lago, Tal1
  • Barkan, Tamar2
  • Morgenstern, Sara2, 3
  • Brook, Elena3
  • Maderer, Annett4
  • Roth, Wilfried4
  • Gordon, Noa1
  • Kashtan, Hanoch2, 5
  • Brenner, Baruch1, 2
  • Moehler, Markus4
  • Aharon, Irit Ben1, 2
  • 1 Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Ze’ev Jabotinsky Rd 39, Petah Tikva, 4941492, Israel , Petah Tikva (Israel)
  • 2 Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801, Israel , Tel Aviv (Israel)
  • 3 Rabin Medical Center, Ze’ev Jabotinsky Rd 39, Petah Tikva, 4941492, Israel , Petah Tikva (Israel)
  • 4 University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, Mainz, 55131, Germany , Mainz (Germany)
  • 5 Beilinson campus, Rabin Medical Center, Ze’ev Jabotinsky Rd 39, Petah Tikva, 4941492, Israel , Petah Tikva (Israel)
Type
Published Article
Journal
BMC Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jan 14, 2020
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12885-020-6517-0
Source
Springer Nature
Keywords
License
Green

Abstract

ObjectiveGastric 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.MethodsGastric 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.ResultsThirty-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).ConclusionOur 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.

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