title: The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B-cell lymphoma patients.
abstract: Epstein-Barr virus (EBV)-encoded small RNA in situ hybridization (EBER-ISH) is a widely accepted method to evaluate EBV involvement in diffuse large B-cell lymphoma (DLBCL), although little is known regarding associations between EBV DNA load and the EBER status and whether EBV DNA load data provide additional clinical information. In this study, we quantified EBV DNA load in diagnostic specimens from DLBCL patients diagnosed at our hospital to evaluate clinical implications of EBV DNA load in diagnostic specimens as contrasted with EBER-ISH. Among 140 DLBCL patients without underlying immunodeficiency, 51 were evaluable for both EBER and EBV DNA load, 83 for EBER only and one for EBV DNA load only. The median EBV DNA load was 708 copies/µg. Although EBV DNA load was significantly higher for EBER-positive patients than for EBER-negative patients (p < 0.001), EBV DNA was detected in up to 72% of EBER-negative patients. Progression-free survival and overall survival were significantly worse for patients with EBV DNA load above 700 copies/µg than for those with EBV DNA load below 700 copies/µg (p = 0.009 and p = 0.003); they were also significantly worse for EBER-positive patients than for EBER-negative patients (p < 0.001 and p = 0.001). Even among EBER-negative patients, higher EBV DNA load conferred worse progression-free survival and overall survival (p = 0.041 and p = 0.013). These findings indicate that EBV DNA load in diagnostic specimens is not a simple surrogate for the EBER status and may be a potential biomarker associated with EBV involvement and prognosis in DLBCL. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Akinao
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yanada
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Inaguma
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Masutaka
authors.initials: M
authors.lastname: Tokuda
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Morishima
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Tadaharu
authors.initials: T
authors.lastname: Kanie
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mizuta
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
authors.affiliation: Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Pathology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Mizoguchi
authors.affiliation: Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Emi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004279:DNA, Viral / Q000097:blood*; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000175:diagnosis*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000175:diagnosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012367:RNA, Viral; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral
keywords: EBER; EBV; EBV DNA load; Epstein-Barr virus; diffuse large B-cell lymphoma