Epstein-Barr virus-associated gastric carcinoma and Epstein-Barr virus infection of the stomach

Lab Invest. 1994 Jul;71(1):73-81.

Abstract

Background: Epstein-Barr virus (EBV) has been found to be associated with a type of gastric carcinoma (EBVaGC). However, many questions remain unanswered, such as epidemiology, and pathologic features of EBVaGC and the significance of EBV in the genesis of EBVaGC.

Experimental design: Gastric carcinoma and non-neoplastic mucosa were evaluated to reveal the following issues: the incidence of EBVaGC in Japanese population, pathologic features and EBV genotype, clonality, and gene-expression in EBVaGC, localization of EBV in non-neoplastic stomach, and serum titer of anti-EBV antibodies in EBVaGC-carrying patients.

Results: Using PCR and EBER1 in situ hybridization, EBVaGC (definitely amplifiable EBV-DNA and positive EBER1-signal in the nuclei of carcinoma cells) was found in 8 of 72 gastric carcinomas (11%). The dominant genotype of EBV was type A (7/8), with type C (6/8), and F (8/8) restriction enzyme polymorphism, which are the predominant type of EBV found in throat washing of the general population in Japan. EBVaGC was found in the cardia (4/8) or body (4/8) of the stomach, and consisted of 7 advanced and 1 intramucosal carcinoma. By Southern blot analysis of EBVaGC hybridized with right- and left-side probe adjacent to the terminal repeats, EBV was present in a monoclonal episomal form in all of the EBVaGC. EBVaGC lacked expression of EBNA2 (0/8) and LMP1 (0/8) by immunocytochemistry. In non-neoplastic mucosa, EBER1 signal was identified in the infiltrating lymphocytes and shedding epithelial cells predominantly in fundic gland mucosa of patients with EBVaGC (8/8). Patients with EBVaGC showed high titers of anti-VCA IgG (8/8), anti-VCA IgA (2/8) and anti-EA IgG (7/8) antibodies just before surgery.

Conclusions: EBV may infect the surface epithelium of the stomach through the reactivated EBV-carrying lymphocytes. EBV may be a factor initiating EBVaGC. Anti-EBV antibodies or EBER1 in situ hybridization may help to identify patients at high risk for EBVaGC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / analysis
  • Base Sequence
  • Burkitt Lymphoma / complications*
  • Carcinoma / microbiology*
  • Carcinoma / pathology
  • DNA, Viral / analysis
  • Gastric Mucosa / microbiology
  • Gene Expression
  • Genotype
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • In Situ Hybridization
  • Molecular Probes / genetics
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Viral / analysis
  • Stomach Neoplasms / microbiology*
  • Stomach Neoplasms / pathology
  • Tumor Virus Infections / complications*

Substances

  • Antibodies, Viral
  • DNA, Viral
  • Molecular Probes
  • RNA, Viral