Direct Evidence for the Presence of Epstein-Barr Virus DNA and Nuclear Antigen in Malignant Epithelial Cells from Patients with Poorly Differentiated Carcinoma of the Nasopharynx

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Abstract
A well-differentiated squamous cell carcinoma and three poorly differentiated carcinomas of the nasopharynx were analyzed for the presence of Epstein-Barr virus DNA by hybridization with radioactive complementary RNA. The well-differentiated carcinoma contained no detectable Epstein-Barr virus DNA, whereas the three anaplastic carcinomas contained 41, 16, and 14 viral genome equivalents per cell. The anaplastic carcinomas were heavily infiltrated with lymphocytes and other non-neoplastic cells. All four tumors were successfully passaged in nude (thymusless) mice. Mouse cell admixture in the heterotransplanted tumors was estimated by analysis of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and varied between 25% and 80%. After two passages in nude mice, the carcinoma that was negative for Epstein-Barr virus DNA remained negative, while the three anaplastic carcinomas retained their viral DNA. After correction for mouse cell admixture, the latter tumors were found to contain about 80, 55, and 160 Epstein-Barr virus genome equivalents per human cell. The virus-determined nuclear antigen was localized in the large carcinoma cell clusters in all three mouse-passaged tumors positive for the viral DNA, but other virus-determined antigens were not detected, indicating the absence of virus induction. In contrast to the original tumor biopsies, the nude-mouse-passaged tumors showed virtually no lymphocytic infiltration. It is concluded that the Epstein-Barr virus DNA found in biopsies of human nasopharyngeal carcinomas is localized in the neoplastic cells.