DETECTION OF EPSTEIN-BARR-VIRUS NUCLEIC-ACID SEQUENCES AND PROTEIN ISNODAL T-CELL LYMPHOMAS - RELATION BETWEEN LATENT MEMBRANE PROTEIN-1 POSITIVITY AND CLINICAL COURSE

Forty-six nodal T-cell lymphomas, classified according to the updated Kiel classification, were investigated for the presence of Epstein-Bar r virus (EBV) DNA by polymerase chain reaction (PCR), EBER 1 and 2 (EB ER 1/2) and latent membrane protein-1 (LMP-1) expression. A combinatio n of RNA in situ hybridization and immunohistochemistry was used to es tablish the phenotype of the Epstein-Barr virus harbouring cells. In 2 1 of 45 cases Epstein-Barr virus DNA sequences could be detected with the polymerase chain reaction. In 15 cases (14 of 2 1 EBV PCR positive cases), EBER 1/2 positive cells could be demonstrated. As judged by m orphology, EBER 1/2 expression was found in non-neoplastic and neoplas tic lymphoid cells. Double staining revealed that more than 80% of the EBER 1/2 harbouring cells, lacked B-, T- or histiocytic markers, sugg esting down regulation of T- and B-cell markers by Epstein-Barr virus. in eight of 15 cases some EBER 1/2 positive T-cells (CD3, CD45RO, CD4 3) morphologically resembling tumour cells were found. In nine of 14 c ases tested EEER 1/2 positive non-neoplastic B-cells (CD20) were seen. Based on in situ hybridization results, four patterns of EBER 1/2 pos itive cells were found, i.e. single cells ( < 1 per medium power field (mpf), n = 3), scattered (1-25/mpf, n = 4), clustered (26-100/mpf, n = 5) and diffuse (> 100/mpf, n = 3). In eight of 15 cases a clustered or diffuse pattern of EBER 1/2 positive cells was found and these lymp homas were therefore considered to be strongly associated with Epstein -Barr virus. In these lymphomas LMP-1 expression was found to be assoc iated with an aggressive clinical course and hepatosplenomegaly.