Clinicopathological Characteristics of Advanced Epstein-Barr Virus-associated Gastric Cancer Highlighting Aberrant p53 Expression

Anticancer Res. 2022 Oct;42(10):4955-4962. doi: 10.21873/anticanres.16002.


Background/aim: Epstein-Barr virus (EBV)-associated gastric cancer is a distinct subtype of stomach adenocarcinoma. Although previous studies have investigated its clinicopathological characteristics, there is a lack of research focusing on advanced EBV-associated gastric cancer. In this study, we performed a comprehensive review of advanced EBV-associated gastric cancer cases.

Patients and methods: We retrospectively collected 18 consecutive cases of surgically resected advanced EBV-associated gastric cancer. Clinicopathological parameters were investigated using histological review, immunohistochemistry, and a review of the electronic medical records of the hospital.

Results: The predominant histological pattern of advanced EBV-associated gastric cancer, according to the Laurén classification, was intestinal-type adenocarcinoma with varying degrees of differentiation. However, focal areas showing conventional gastric carcinoma with a lymphoid stromal pattern were found in all cases except one. In addition to the previously described histological patterns of EBV-associated gastric cancer, one case displayed chronic granulomatous inflammation-like histology with barely identifiable malignant epithelial cells. Another case had a pure signet-ring cell carcinoma component showing nuclear positivity for the EBV-encoded RNA in situ hybridization assay. Remarkably, five out of 18 cases (27.8%) showed aberrant p53 expression on immunostaining, which is known to occur rarely in EBV-associated gastric cancer. All cases with aberrant p53 expression had intestinal-type adenocarcinoma-like components.

Conclusion: Advanced EBV-associated gastric cancer had distinct histology and a higher rate of aberrant p53 immunostaining pattern than conventional EBV-associated gastric cancer. Therefore, their biological behavior should be investigated separately.

Keywords: Epstein–Barr virus; advanced gastric cancer; gastric carcinoma with lymphoid stroma; p53.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma* / pathology
  • Epstein-Barr Virus Infections*
  • Herpesvirus 4, Human / genetics
  • Humans
  • RNA
  • Retrospective Studies
  • Stomach Neoplasms* / pathology
  • Tumor Suppressor Protein p53


  • Tumor Suppressor Protein p53
  • RNA