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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. Danish Lymphoma Study
Group, LYFO
F d'Amore, P Johansen, A Houmand, DD Weisenburger and LS Mortensen
Department of Hematology, Odense University Hospital, Denmark.
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 < .00005)
cases, but in only 1 of 16 cases with non- B/non-T-cell or undetermined
phenotype. Among T-NHL cases, EBER positivity was confined to
angioimmunoblastic, lymphadenopathy-like lymphoma (11 of 13 cases, 85%),
Lennert's lymphoma (five of seven cases, 71%), and pleomorphic T-NHL (24 of
67 cases, 36%). Mycosis fungoides, lymphoblastic, and CD30-positive
anaplastic large T-cell NHL cases were consistently EBV-negative.
Double-labeling by RISH and immunophenotyping demonstrated the presence of
EBV in neoplastic T cells, but no CD21 expression was found in the
EBER-positive T-NHL cases. LMP-1 was expressed in 12 of 40 (30%)
EBER-positive T-NHL and 5 of 25 (20%) EBER-positive B-NHL cases. For both
T- and B-NHL, no correlation was found for EBER positivity and age, sex,
clinical stage, or serum level of lactate dehydrogenase (LDH) at diagnosis.
However, in T-NHL but not B-NHL, EBER positivity correlated with the
presence of constitutional symptoms and a poor performance score (PS <
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.
Volume 87,
Issue 3,
pp. 1045-1055,
02/01/1996
Copyright © 1996 by The American Society of Hematology
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