Different lines of evidence support an association between Epstein-Barr virus (EBV) and
gastric cancer (GC). The main understood risk factor to develop GC is
infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from
gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of
infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in
cancer progression, we analyzed 75 samples of GC, 147 control samples of non-
tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-
atrophic gastritis (NAG). A first-round PCR was used for EBV detection in
tumor and non-
tumor controls and a more sensitive nested PCR for
gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-
tumor controls and 8% of
gastritis samples were found positive. An
EBER1 in situ hybridization showed
EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs
infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger.