Evidence of Epstein-Barr Virus Association with Gastric Cancer and Non-Atrophic Gastritis

Abstract

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.

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

“…Another study involving 53 Brazilian patients from the State of São Paulo revealed 11.3% positivity, with male predominance (83.3%), median age of 59 years and a higher incidence of lesions in the gastric antrum (41.5%) (41) . Similarly, a prevalence of 9.6% was found in 39 patients from the City of Belém, State of Pará (20) , and another study, also involving a population from Northern Brazil, but including only ten GC patients and six controls without tumor, found that eight patients had EBV DNA in their tumor cells, with no positivity in the control group (22) . There is no data available about the prognostic value of EBV infection in the Brazilian population.…”

“…In healthy individuals, infection of the gastric epithelial cells is rare (20) (21) (22) , and the mechanisms underlying infection of the gastric mucosa by EBV remain unknown. It is assumed that EBV infection is an early event in carcinogenesis, owing to evidence of virus infection in premalignant lesions, such as dysplastic epithelial cells (2) (21) (23) .…”

Co-infection withHelicobacter pyloriand Epstein–Barr virus in benign upper digestive diseases: An endoscopic and serologic pilot study

“…15 Initially, EBV was found only in lymphocytes infiltrating gastric tumours; later its presence was demonstrated in non-atrophic and non-metaplastic mucosa. 16 Much less is known about EBV in benign upper gastrointestinal diseases. Lymphocytes are only rarely seen in normal (i.e.…”

Development of a time-resolved fluoroimmunoassay for Epstein–Barr virus viral capsid antigen IgA antibody in human serum

“…At present, nested PCR and quantitative real-time PCR are commonly used Lin et al, 2014;Martinez-Lopez et al, 2014;Sousa et al, 2011). Nucleic acid diagnosis can indicate the existence of a viral genome and provides direct results, with the advantages of high sensitivity, specificity and quantitative monitoring.…”