Expression of latent membrane protein 1 in clinically isolated cases and animal models of AIDS-associated non-Hodgkin's lymphomas.

Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is known to be expressed in non-Hodgkin's lymphomas (NHL) occurring in immunocompromised hosts, playing crucial roles in lymphomagenesis. LMP1 expression at the microscopic level, however, was reported to be limited to some, not all, neoplastic cells in each specimen studied. In order to determine whether LMP1 expression of NHL really is limited to some cells, five clinically isolated acquired immunodeficiency syndrome (AIDS)-associated and six experimental NHL were studied immunohistochemically, immuno-electron microscopically and flow cytometrically. The experimental models were the lymphocytic tumors produced in severe combined immune deficiency (SCID) mice after engrafting EBV-infected B cells. Light microscopy revealed intense LMP1-immunostaining in less than 5% of neoplastic cells in the NHL, weak staining in less than 50% and apparently unstained cells in over 50%. Immuno-electron microscopy revealed that the intensely stained cells were those undergoing degeneration, whereas a proportion of the remainder demonstrated patchy reactions on their cell membranes. The weakly stained cells were found to correspond to cells with several patches on their cell membranes. Flow-cytometric analysis demonstrated that a large proportion of the neoplastic cells expressed LMP1 to some extent. Taken together, the results suggest that most of the neoplastic cells expressed LMP1 molecules at quantitatively different levels, some of which were below the level detectable by light microscopy. The intensely stained cells were shown to be those undergoing degeneration.