Epstein-Barr virus in gastric carcinoma with lymphoid stroma. Special reference to its detection by the polymerase chain reaction and in situ hybridization in 99 tumors, including a morphologic analysis

Cancer. 1994 May 1;73(9):2239-49. doi: 10.1002/1097-0142(19940501)73:9<2239::aid-cncr2820730902>3.0.co;2-#.


Background: Gastric carcinoma with lymphoid stroma (GCLS) has been reported to have a more favorable prognosis than ordinary gastric carcinoma, however, the precise mechanism of the pathogenesis for GCLS remains unclear.

Methods: The authors analyzed 99 GCLS in 94 patients for Epstein-Barr virus (EBV) sequences using polymerase chain reaction (PCR) and in situ hybridization (ISH); these were compared with 42 ordinary gastric carcinomas.

Results: Two series of PCR showed 81 (82%) and 46 (47%) of the 99 GCLS to have EBV sequences, which were significantly higher compared with ordinary gastric carcinoma (50% and 9.5%, respectively). With ISH using thymine-thymine dimerized oligonucleotide probes corresponding to EBV-encoded small RNA 1 (EBER1), 82 (83%) of 99 GCLS showed clear, intense hybridization signals localized over the nuclei of the tumor cells, in contrast to only 4 (9.5%) of 42 ordinary carcinomas (P < 0.001). A comparative morphologic analysis of EBER1-positive and negative GCLS revealed that typical features of GCLS, such as mild cellular pleomorphism, rare mitoses, a marked degree of lymphoid stroma, and mild fibrosis, together with a lymphoid infiltration within the cancer cell nests were significantly more frequent in EBER1-positive GCLS.

Conclusions: More than 80% of GCLS were associated with EBV. The presence of EBV association in GCLS was characterized by the above morphologic features.

MeSH terms

  • Adenocarcinoma / microbiology
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / microbiology*
  • Carcinoma / pathology*
  • Cell Nucleus / ultrastructure
  • DNA Probes
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Female
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • In Situ Hybridization*
  • Lymphoid Tissue / microbiology
  • Lymphoid Tissue / pathology
  • Male
  • Middle Aged
  • Mitosis
  • Polymerase Chain Reaction*
  • Prognosis
  • Stomach Neoplasms / microbiology*
  • Stomach Neoplasms / pathology*
  • Survival Rate


  • DNA Probes
  • DNA, Viral