Epstein-Barr-virus-associated medullary carcinomas with lymphoid infiltration of the stomach.

The association of Epstein-Barr virus (EBV) with gastric medullary carcinoma with lymphoid infiltration (GMCL) was investigated. The presence of GMCL exhibited a 2/1 male-to-female ratio and a 1/2 early-to-advanced cancer ratio, predominantly located in the cardia and corpus of the stomach (90%). The presence of EBV DNA could be proven in 28 out of 30 GMCL cases (93%) by the polymerase chain reaction method, and in 27 cases (90%) latent infection of EBV strictly limited to cancer cells was identified by in situ hybridization with RNA using an EBV-associated small RNAs (EBERs) probe. No histopathological difference was noted between EBERs-positive and -negative groups. Monoclonal EBV infection, identified by the length of lymphocyte-determined membrane antigen variable tandem repeats, was suggested in 19 out of 27 EBERs-positive cases (70.3%). However, only one case showed a positive reaction for anti-(latent membrane protein)-1 antibody, and none of the EBERs-positive cases bound anti-EBNA-2 antibodies, the respective antigens being considered oncoproteins directly linked with EBV-related B cell lymphomagenesis. In conclusion, while EBV is clearly present at extremely high incidence in GMCL, having characteristics biological features, a role for EBV in tumorigenesis of such lesions remains uncertain.