FREQUENT DETECTION OF EPSTEIN-BARR-VIRUS (EBV), EBEB TRANSCRIPTS AND LATENT MEMBRANE PROTEIN-1 (LMP-1) IN TUMOR-CELLS IN HODGKINS-DISEASE ARISING IN CHILDHOOD

Paraffin sections from 22 cases of Hodgkin's disease (HD) and 30 cases of non-Hodgkin's lymphomas (NHL) occurring in childhood (3-15 years o ld) were examined for the presence of Epstein-Barr Virus (EBV) encoded EBER mRNAS and Latent Membrane Protein-1 (LMP-1) using RNA in situ hy bridization (RISH) and immunohistochemistry, respectively. In 12/22 (5 4%) cases of HD the EBER transcripts were detected in most Reed-Sternb erg and Hodgkin (HRS) cells as well as in some scattered smaller lymph oid cells. In all these cases the LMP-1 protein was detected exclusive ly in HRS cells. Three additional cases of HD were found to be EBER RI SH positive only in a few scattered small lymphoid cells, the LMP-1 st aining being negative in these cases. The EBER and LMP-1 positivity in HRS cells were present in 0/1 of lymphocyte predominant, 4/10 (40%) o f nodular sclerosis and 8/11 (72%) of mixed cellularity of HD. No EBER RISH signal tr,as found in tumor cells of the 30 cases of NHL. In fou r of them only a few scattered small lymphoid cells were EBER RISH pos itive. LMP-I reactivity was not detected in any NHL. These results pro vide evidence for an association between EBV and a sizeable proportion of childhood Hodgkin's disease and show that this association is move frequent in mixed cellularity subtype. Furthermore, the detection of the LMP-1 protein in HRS cells in view of the LMP-1 transforming poten tial, suggests that EBV may be involved in the pathogenesis of a subst antial proportion of cases of HD occurring in childhood.