DETECTION OF EPSTEIN-BARR-VIRUS IN MULTIPLE SITES INVOLVED BY HODGKINS-DISEASE

Tissues obtained from 14 patients with multiple anatomic sites involve d by Hodgkin's disease were studied for Epstein-Barr virus (EBV using in situ hybridization for EBV-encoded RNA (EBER) I and immunohistochem ical methods for EBV latent membrane protein (LMP) expression. Each pa tient in this study had two to five separately involved anatomic sites , and all biopsy sites, a total of 43 specimens, were analyze for EBV. EBV was detected in 6 of 14 (42.8%) patients with Hodgkin's disease, including 5 of 11 (45.4%) with nodular sclerosis and 1 of 3 (33%) with wired cellularity In these six patients, all biopsy sites were positi ve for both EBER1 and LMP. In the EBV-positive eases we analyzed the 3 '-end of the EBV LMP1 gene in all sites of disease using polymerase ch ain reaction. In three patients all sites of disease bad a 30-base pai r deletion In two patients, there was discordance between sites of dis ease, with LMP1 gene deletions in some sites and other sites with the LMP1 gene in the germline configuration. The results of this study dem onstrate that EBV, when found ht Hodgkin's disease, is detectable in a ll anatomic sites involved The presence of the same 30-base pair delet ion an the EBV LMP1 gene in all sites of disease in three patients sug gests that the deletion occurred before dissemination and that all sit es are clonally related. However, the discordance between anatomic sit es in two patients suggests that LMP1 gene deletion may also occur as a later event, rafter dissemination These results lend further support to the hypothesis that EBV plays a role in the pathogenesis of a subs et of cases of Hodgkin's disease.