EXPRESSION OF EPSTEIN-BARR-VIRUS LATENT GENE-PRODUCTS IN TUMOR-CELLS OF HODGKINS-DISEASE

The Epstein-Barr virus (EBV)-encoded latent gene products, latent membrane protein (LMP) and EBV nuclear antigen 2 (EBNA 2), seem to have important roles in EBV-induced cell transformation in vitro, and have been implicated as important effector molecules in EBV-associated lymphomagenesis. Because up to 35% of Hodgkin's disease (HD) samples have been reported to contain EBV genomes, the expression of LMP and EBNA 2 in these tumours was investigated. 84 cases of HD were studied with monoclonal antibodies and immunohistochemical labelling of acetone-fixed cryostat sections. LMP, but not EBNA 2 was demonstrated in Reed-Sternberg (RS) cells of 40 cases (48%); the two proteins were easily detected in transformed lymphocytes of positive control acute infectious mononucleosis tonsils. LMP expression in RS cells varied according to the histological subtype of HD (1/10 cases [10%] of lymphocyte predominance subtype, 16/50 cases [32%] of nodular sclerosis, 23/24 [96%] cases of mixed cellularity type). That the LMP antibodies showed no substantial cross-reactivity with negative control tissues shows that they are useful probes for the diagnosis of latent EBV infection in tissue sections. The finding suggest that EBV is associated with more cases of HD than was previously recognised, that in positive cases RS cells express a latent infection protein phenotype (LMP +, EBNA 2-) which differs from that of other EBV-associated lymphomas, and the LMP expression is related to histologically aggressive subtypes of HD.