Background: Gastric carcinoma with lymphoid stroma (GCLS), known to have a more favorable prognosis than ordinary gastric carcinoma, has been suggested to be closely associated with the Epstein-Barr virus (EBV). However, there are many clinicopathologic problems that remain unsolved.
Methods: In 21 patients, 26 GCLS lesions and 4 non-GCLS intramucosal adenocarcinomas that developed synchronously or metachronously with GCLS were examined for EBV involvement by in situ hybridization (ISH) and were analyzed clinicopathologically. In addition, nine patients who had advanced gastric carcinoma with massive liver metastases, who showed good response to chemotherapy and had prolonged survival, were examined for the presence or absence of EBV-associated GCLS.
Results: On ISH with EBV-encoded small RNAs, diffuse hybridization signals were noted in 22 (84.6%) of 26 GCLS. Hybridization signals were also noted in all four non-GCLS adenocarcinomas accompanying GCLS. As a result, hybridization signals were noted in nine of ten cancerous lesions in four cases of synchronous multiple cancers and in all five cancerous lesions in two cases of metachronous multiple cancers. Long term survivors with liver metastases included two patients with EBV-associated GCLS.
Conclusion: Approximately 84.6% of GCLS were related to EBV. EBV-associated GCLS constitutes one-half of the EBV-infected stomach cancers in our institution. The complete response and long term survival after conventional chemotherapy of two patients with Stage IV GCLS suggests that this form of gastric carcinoma may be especially sensitive to this treatment. The identification of EBV-associated synchronous multicentric cancers of both GCLS and non-GCLS type suggests that EBV infection may be an early event in the induction process of these tumors.