Epstein-Barr virus genome in non-Hodgkin's lymphomas occurring in immunocompetent patients: Highest prevalence in nonlymphoblastic T-cell lymphoma and correlation with a poor prognosis

Abstract

A series of 520 cases of non-Hodgkin's lymphoma (NHL; 374 of B-cell, 130 of T-cell, 5 of non-B/non-T-cell, and 11 of undetermined phenotype) was analyzed for the presence of Epstein-Barr virus (EBV) using RNA in situ hybridization (RISH). The aims of the study were to assess the frequency of EBV-encoded small nuclear RNAs 1 and 2 (EBER), abundant immediate early RNAs (BHLF), and latent membrane protein-1 (LMP-1) in cases covering the entire histologic spectrum of NHL, and to analyze whether EBV status had prognostic relevance with regard to patient survival. EBER positivity was found in 25 of 374 (7%) B-NHL and 40 of 130 (31%) T-NHL (P 1; scale, 0 to 4). EBER status did not have any prognostic significance in B-NHL, but it had a negative prognostic impact in high-grade T-NHL (7-year survival of EBER-negative v EBER-positive cases: 33% v 14%; P = .01). A multivariate analysis including all B- and T-NHL of intermediate-/high-grade histology showed that EBER positivity in T-NHL was one of the three most significant factors recognized by the final prognostic model, only surpassed by PS greater than 1 and age greater than 67 years, and more powerful than B symptoms, an elevated LDH, or disseminated disease (clinical stage greater than II). We conclude that patients with EBV-positive T-NHL have a very poor clinical outcome, that EBV status should be considered as additional useful information in the classification of T-NHL, and that EBV-positive T-NHL should be treated as a separate entity in the future.