title: Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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. Clin Cancer Res; 20(9); 2338-49. ©2014 AACR.
authors.affiliation: Authors' Affiliations: Departments of Hematopathology and Biostatistics and Bioinformatics, The University of Texas MD Anderson Cancer Center; The Methodist Hospital, Houston, Texas; Memorial Sloan-Kettering Cancer Center; Weill Medical College of Cornell University; Columbia University Medical Center and New York Presbyterian Hospital, New York, New York; University of North Carolina School of Medicine, Chapel Hill, North Carolina; Cleveland Clinic, Cleveland, Ohio; University of California San Francisco School of Medicine, San Francisco, California; Gundersen Lutheran Health System, La Crosse, Wisconsin; Feinberg School of Medicine, Northwestern University, Chicago, Illinois; San Bartolo Hospital, Vicenza; San Raffaele H. Scientific Institute, Milan, Italy; University Hospital, Basel, Switzerland; Hospital Universitario Marques de Valdecilla, Santander, Spain; Aalborg University Hospital, Aalborg; Odense University Hospital, Odense, Denmark; Medical School of Taizhou University, Taizhou, Zhejiang; University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China; Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea.
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Ok
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Zijun Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.forename: Alexander
authors.initials: A
authors.lastname: Tzankov
authors.forename: Ganiraju C
authors.initials: GC
authors.lastname: Manyam
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkaer
authors.forename: Karen
authors.initials: K
authors.lastname: Dybaer
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Richards
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: William W L
authors.initials: WW
authors.lastname: Choi
authors.forename: J Han
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Jooryung
authors.initials: J
authors.lastname: Huh
authors.forename: Weiyun
authors.initials: W
authors.lastname: Ai
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: John P
authors.initials: JP
authors.lastname: Farnen
authors.forename: Michael B
authors.initials: MB
authors.lastname: Møller
authors.forename: Carlo E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.forename: Roberto N
authors.initials: RN
authors.lastname: Miranda
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016000:Cluster Analysis; D003520:Cyclophosphamide / Q000627:therapeutic use; D019049:Developed Countries / Q000706:statistics & numerical data; D004317:Doxorubicin / Q000627:therapeutic use; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009367:Neoplasm Staging; D010766:Phosphorylation; D011241:Prednisone / Q000627:therapeutic use; D015995:Prevalence; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D017730:Ki-1 Antigen; D016328:NF-kappa B; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone