title: Immunophenotypic characterization of Epstein-Barr virus-associated gastric carcinoma: massive infiltration by proliferating CD8+ T-lymphocytes.
abstract: A subset of gastric carcinoma carries Epstein-Barr virus (EBV). The immunophenotypic features of EBV-associated (EBV+) gastric carcinoma, which we have analyzed using 25 EBV+ cases, remain unclear. Frozen tissue samples were stained with antibodies to various immune cell markers. To evaluate the proliferative activity of CD8+ cells, we performed CD8/Ki-67 double staining on paraffin-embedded sections. The results were compared with those in EBV-negative (EBV-) gastric carcinomas. All EBV+ and EBV- gastric carcinoma cells expressed major histocompatibility complex class I, whereas major histocompatibility complex class II expression in tumor cells was more prominent in EBV+ cases. Intercellular adhesion molecule-1 and Fas/APO-1 expression was largely restricted to EBV+ cases. The lymphocytes that infiltrated EBV+ tumor nests were predominantly CD8+ T cells, many of which expressed perforin. Immunoelectron microscopy confirmed a close cell to cell contact between these CD8+ cells and carcinoma cells. CD8+ cells were CD11a+ and CD11b- by flow cytometry performed in one case. The labeling index of Ki-67, the proliferation-associated antigen, in CD8+ cells was 4 times higher in EBV+ cases than in EBV- cases. Our data suggest that these CD8+ cells, which bear a cytotoxic phenotype, are actively proliferating in close contact with EBV+ tumor cells and that the specificity of the CD8+ cells may be directed to EBV and/or cellular antigens expressed by the tumor. This is consistent with a generally favorable prognosis of EBV+ gastric carcinoma. Because the observed T-cell infiltration is insufficient to eradicate the tumor cells, certain immunosuppressive factors were speculated to allow the essentially immunogenic carcinoma cells to establish a macroscopic lesion.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Saiki
authors.forename: H
authors.initials: H
authors.lastname: Ohtani
authors.forename: Y
authors.initials: Y
authors.lastname: Naito
authors.forename: M
authors.initials: M
authors.lastname: Miyazawa
authors.forename: H
authors.initials: H
authors.lastname: Nagura
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D002452:Cell Count; D002455:Cell Division; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D016253:Microscopy, Immunoelectron; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D014412:Tumor Virus Infections / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules