Macrophage involvement in Epstein-Barr virus-related tumors

Epstein-Barr virus (EBV) is known as a causative agent of Burkitt's lymphoma, nasopharyngeal carcinoma and approximately 10% of stomach carcinoma cases. In other human cancers, EBV gene expression including lytic infection protein detected using in situ hybridization and immunofluorescence staining has been reported. Moreover, the expression and replication of EBV genes in cultured normal macrophages and in histiocytes of Langerhans' cell histiocytosis have been identified. The aim of this study was to examine EBV expression in macrophages in other EBV-associated human tumors. Forty-one cases of EBV-associated tumors, which had been confirmed to express EBV, were examined. Tissue sections after in situ hybridization were double-stained immunohistochemically with the monoclonal anti-CD68 antibody. EBV expression in macrophages in the lesions of nasopharyngeal carcinoma, oral cancer, thyroid carcinoma, renal cell carcinoma, testicular carcinoma, uterine carcinoma, cutaneous T-cell lymphoma and anaplastic large-cell lymphoma was identified, whereas macrophages in normal or non-cancerous lesions showed no EBV expression. Many tumor-associated macrophages in EBV-related tumors carry EBV, which appears to induce the EBV lytic infection of macrophages. Therefore, the possibility that the lytic infection of macrophages by EBV and the resulting inflammation play certain roles in the oncogenesis of EBV-associated human tumors was raised.