Frequent detection of Epstein-Barr virus (EBV), EBER transcripts and latent membrane protein-1 (LMP-1) in tumor cells in Hodgkin's 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 old) were examined for the presence of Epstein-Barr Virus (EBV) encoded EBER mRNAS and Latent Membrane Protein-1 (LMP-1) using RNA in situ hybridization (RISH) and immunohistochemistry, respectively. In 12/22 (54%) cases of HD the EBER transcripts were detected in most Reed-Sternberg and Hodgkin (HRS) cells as well as in some scattered smaller lymphoid cells. In all these cases the LMP-1 protein was detected exclusively in HRS cells. Three additional cases of HD were found to be EBER RISH positive only in a few scattered small lymphoid cells, the LMP-1 staining 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%) of nodular sclerosis and 8/11 (72%) of mixed cellularity of HD. No EBER RISH signal was found in tumor cells of the 30 cases of NHL. In four of them only a few scattered small lymphoid cells were EBER RISH positive. LMP-1 reactivity was not detected in any NHL. These results provide evidence for an association between EBV and a sizeable proportion of childhood Hodgkin's disease and show that this association is more frequent in mixed cellularity subtype. Furthermore, the detection of the LMP-1 protein in HRS cells in view of the LMP-1 transforming potential, suggests that EBV may be involved in the pathogenesis of a substantial proportion of cases of HD occurring in childhood.