PRESENCE OF EPSTEIN-BARR-VIRUS LATENCY TYPE-III AT THE SINGLE-CELL LEVEL IN POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS AND AIDS-RELATED LYMPHOMAS

Aims-To investigate the expression pattern of Epstein-Barr virus (EBV) latent genes at the single cell level in posttransplantation lymphopr oliferative disorders and acquired immunodefiency syndrome (AIDS) rela ted lymphomas, in relation to cellular morphology. Methods-Nine post-t ransplantation lymphoproliferative disorders and three AIDS related ly mphomas were subjected to immunohistochemistry using monoclonal antibo dies specific for EBV nuclear antigen 1(EBNA1) (2H4), EBNA2 (PE2 and t he new rat anti-EBNA2 monoclonal antibodies 1E6, R3, and 3E9), and LMP 1 (CS1-4 and S12). Double staining was performed combining R3 or 3E9 w ith S12. Results-R3 and 3E9 anti-EBNA2 monoclonal antibodies were more sensitive than PE2, enabling the detection of more EBNA2 positive lym phoma cells. Both in post-transplantation lymphoproliferative disorder s and AIDS related lymphomas, different expression patterns were detec ted at the single cell level. Smaller neoplastic cells were positive f or EBNA2 but negative for LMP1. Larger and more blastic neoplastic cel ls, sometimes resembling Reed-Sternberg cells, were LMP1 positive but EBNA2 negative (EBV latency type II). Morphologically intermediate neo plastic cells coexpressing EBNA2 and LMP1 (EBV latency type III), were detected using R3 and 3E9, and formed a considerable part of the neop lastic population in four of nine post-transplantation lymphoprolifera tive disorders and two of three AIDS related lymphomas. All samples co ntained a subpopulation of small tumour cells positive exclusively for Epstein-Barr early RNA and EBNA1. The relation between cellular morph ology and EBV expression patterns in this study was less pronounced in AIDS related lymphomas than in post-transplantation lymphoproliferati ve disorders, because the AIDS related lymphomas were less polymorphic than the post-transplantation lymphoproliferative disorders. Conclusi ons-In post-transplantation lymphoproliferative disorders and AIDS rel ated lymphomas, EBV latency type III can be detected by immunohistoche mistry in a subpopulation of tumour cells using sensitive monoclonal a ntibodies R3 and 3E9. Our data suggest that EBV infected tumour cells in these lymphomas undergo gradual changes in the expression of EBV la tent genes, and that these changes are associated with changes in cell ular morphology.