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Epstein-Barr virus DNA is abundant and monoclonal in the Reed-Sternberg
cells of Hodgkin's disease: association with mixed cellularity subtype and
Hispanic American ethnicity
ML Gulley, PA Eagan, L Quintanilla-Martinez, AL Picado, BN Smir, C Childs, CD Dunn, FE Craig, JW Williams and PM Banks
Department of Pathology, University of Texas Health Science Center, San
Antonio 78284-7750.
One hundred twenty-five cases of Hodgkin's disease from the United States
(79), Mexico City (31), and Costa Rica (15) were analyzed for the presence
of Epstein-Barr virus (EBV) by in situ hybridization to EBER1 transcripts.
EBV was more frequently detected in the Reed- Sternberg (RS) cells of mixed
cellularity Hodgkin's disease (37 of 48 [77%]) compared with the nodular
sclerosis subtype (19 of 71 [27%], P < .001). The presence of EBV was
also associated with Hispanic ethnicity (P < .001). In a multivariate
analysis, patient age, gender, and geographic location were less predictive
of EBV positivity than were mixed cellularity histology (odds ratio = 8.3)
and Hispanic ethnicity (odds ratio = 4.3). Southern blot analysis of EBV
terminal repeat fragments using the Xho1a probe showed that the viral DNA
was monoclonal in 17 of 17 cases having EBER1-positive RS cells. By
comparison, EBV DNA was not detected by Southern analysis in 20 cases
lacking EBER1 in RS cells, even when occasional background lymphocytes
expressed EBER1. Because clonal viral DNA was so readily detected in
EBER1-positive cases, the EBV genome is probably amplified at least 50-
fold in the infected RS cells. Monoclonality of EBV DNA implies that the RS
cells were infected before malignant transformation.
Volume 83,
Issue 6,
pp. 1595-1602,
03/15/1994
Copyright © 1994 by The American Society of Hematology

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