Morphological evidence of an activated cytotoxic T-cell infiltrate in EBV-positive gastric carcinoma preventing lymph node metastases

Am J Surg Pathol. 2006 Jan;30(1):59-65. doi: 10.1097/01.pas.0000176428.06629.1e.


Recently, we showed that Epstein-Barr virus (EBV)-positive gastric carcinoma (GC) forms a distinct clinicopathologic entity with a better prognosis due to lower incidence of lymph node metastases (LN+). Here we investigated whether in EBV-positive GC more pronounced activation of cellular immune responses is associated with absence of (micro)metastases. Twenty EBV-positive primary tumors (PT) (9 LN+) were matched with 28 EBV-negative GC (11 LN+) for T- and N-stage, gender, and age. The PT (n = 28) and its LNs were analyzed by EBER RNA in situ hybridization and by immunohistochemistry for MHC class I and II expression, for CD3, CD8, CD4, CD20, CD56, CD83, and Granzyme B (GzB) expression. In LN metastases of EBV-positive GC, the EBV genome is maintained, excluding tumor escape by virus deletion. All GC express MHC class I independently of EBV status. In comparison with EBV-negative GC, EBV-positive GC have higher expression of MHC class II on the tumor cells (P = 0.029) and a more extensive infiltrate (P < 0.0001) of activated GzB+ CD8+ T cells (P = 0.028), which is most abundant in those EBV-positive tumors that do not metastasize (P < 0.0001). In addition, in EBV-positive GC without metastases, the infiltrate contains higher numbers of mature dendritic cells (DC) (P = 0.018). At present, the antigenic target has to be determined. These data support the notion that local triggering of cellular immune responses in EBV-positive GC prevents lymph node metastasis formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / virology
  • Biomarkers, Tumor / analysis
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Lymphatic Metastasis / immunology*
  • Lymphatic Metastasis / pathology
  • Lymphocyte Subsets / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / virology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Virus Infections / immunology*


  • Biomarkers, Tumor