DECREASED EXPRESSION OF CELLULAR MARKERS IN EPSTEIN-BARR VIRUS-POSITIVE HODGKINS-DISEASE

Epstein-Barr virus (EBV) has been demonstrated in the Reed-Sternberg cells and their mononuclear variants (Hodgkin cells; H-RS cells) in a substantial number of Hodgkin's disease (HD) cases. Moreover, EBV can modulate both in vivo and in vitro the expression of several cellular genes, including lymphoid differentiation markers. Therefore we investigated, in 64 cases of HD, the relationship between the presence of EBV and the expression of lymphoid (CD45RB), T- (CD3, CD45RO), B- (CD20, MB2 antigen, CDw75), and myeloid-cell lineage markers (CD15), and of activation markers (CD30, EMA, and the 115D8 antigen) on the H-RS cells. EBV-positive cases, as demonstrated by the presence of EBER-1 and -2 RNA and LMP-1 protein expression, showed a significant reduction in the expression on H-RS cells of T-cell lineage (CD3, P < 0.02), B-cell lineage (CD20; P < 0.005), and activation markers (EMA; P < 0.002 and the 115D8 antigen; P < 0.001) as compared with EBV-negative cases. No differences were found in the expression of CD15, CD30, CD45RO, CD45RB, CDw75, or the MB2 antigen on H-RS cells in EBV-positive and EBV-negative HD cases. Interestingly, in 11 cases of EBV-negative HD, B- as well as T-cell lineage markers could be found on some H-RS cells. These data suggest that EBV in H-RS cells is able to down-regulate the expression of T- (CD3) and B- (CD20) cell lineage markers and lymphoid activation markers (EMA and the 115D8 antigen). For this reason, the origin of H-RS cells in HD, as studied by immunohistochemistry, cannot be discussed without taking into account the presence of EBV.