TY - JOUR
T1 - Prevalence and clinical implications of Epstein-Barr virus infection in de Novo diffuse large B-cell lymphoma in western countries
AU - Ok, Chi Young
AU - Li, Ling
AU - Xu-Monette, Zijun Y.
AU - Visco, Carlo
AU - Tzankov, Alexander
AU - Manyam, Ganiraju C.
AU - Montes-Moreno, Santiago
AU - Dybaer, Karen
AU - Chiu, April
AU - Orazi, Attilio
AU - Zu, Youli
AU - Bhagat, Govind
AU - Chen, Jiayu
AU - Richards, Kristy L.
AU - Hsi, Eric D.
AU - Choi, William W.L.
AU - Van Krieken, J. Han
AU - Huh, Jooryung
AU - Ai, Weiyun
AU - Ponzoni, Maurilio
AU - Ferreri, Andrés J.M.
AU - Farnen, John P.
AU - Møller, Michael B.
AU - Bueso-Ramos, Carlo E.
AU - Miranda, Roberto N.
AU - Winter, Jane N.
AU - Piris, Miguel A.
AU - Medeiros, L. Jeffrey
AU - Young, Ken H.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/5/1
Y1 - 2014/5/1
N2 - Purpose: Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV+ DLBCL, independent of age, treated with rituximab combined with CHOP (R-CHOP) in developed Western countries. Experimental design: A large cohort (n = 732) of patients with DLBCL treated with R-CHOP chemotherapy is included from the multicenter consortium. This study group has been studied for expression of different biomarkers by immunohistochemistry, genetic abnormalities by FISH and mutation analysis, genomic information by gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results: Twenty-eight patients (4.0%) were positive for EBV with a median age of 60.5 years. No clinical characteristics distinguished patients with EBV+ DLBCL from patients with EBV-negative (EBV-) DLBCL. Genetic aberrations were rarely seen. NF-κB p50, phosphorylated STAT-3, and CD30 were more commonly expressed in EBV+ DLBCLs (P < 0.05). Significant differences in survival were not observed in patients with EBV+ DLBCL versus EBV-DLBCL. However, CD30 expression combined with EBV conferred an inferior outcome. GEP showed a unique expression signature in EBV+ DLBCL. GSEA revealed enhanced activity of the NF-κB and JAK/STAT pathways independent of molecular subtype. Conclusions: The clinical characteristics of patients with EBV+ versus EBV-DLBCL are similar and EBV infection does not predict a worse outcome. EBV+ DLBCL, however, has a unique genetic signature. CD30 expression is more common in EBV+ DLBCL and, consistent CD30 and EBV is associated with an adverse outcome.
AB - Purpose: Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV+ DLBCL, independent of age, treated with rituximab combined with CHOP (R-CHOP) in developed Western countries. Experimental design: A large cohort (n = 732) of patients with DLBCL treated with R-CHOP chemotherapy is included from the multicenter consortium. This study group has been studied for expression of different biomarkers by immunohistochemistry, genetic abnormalities by FISH and mutation analysis, genomic information by gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results: Twenty-eight patients (4.0%) were positive for EBV with a median age of 60.5 years. No clinical characteristics distinguished patients with EBV+ DLBCL from patients with EBV-negative (EBV-) DLBCL. Genetic aberrations were rarely seen. NF-κB p50, phosphorylated STAT-3, and CD30 were more commonly expressed in EBV+ DLBCLs (P < 0.05). Significant differences in survival were not observed in patients with EBV+ DLBCL versus EBV-DLBCL. However, CD30 expression combined with EBV conferred an inferior outcome. GEP showed a unique expression signature in EBV+ DLBCL. GSEA revealed enhanced activity of the NF-κB and JAK/STAT pathways independent of molecular subtype. Conclusions: The clinical characteristics of patients with EBV+ versus EBV-DLBCL are similar and EBV infection does not predict a worse outcome. EBV+ DLBCL, however, has a unique genetic signature. CD30 expression is more common in EBV+ DLBCL and, consistent CD30 and EBV is associated with an adverse outcome.
UR - http://www.scopus.com/inward/record.url?scp=84899764939&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899764939&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-13-3157
DO - 10.1158/1078-0432.CCR-13-3157
M3 - Article
C2 - 24583797
AN - SCOPUS:84899764939
VL - 20
SP - 2338
EP - 2349
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 9
ER -