The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B-cell lymphoma patients

Akinao Okamoto, Masamitsu Yanada, Yoko Inaguma, Masutaka Tokuda, Satoko Morishima, Tadaharu Kanie, Yukiya Yamamoto, Shuichi Mizuta, Yoshiki Akatsuka, Tetsushi Yoshikawa, Yoshikazu Mizoguchi, Shigeo Nakamura, Masataka Okamoto, Nobuhiko Emi

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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 EBERnegative 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.

Original languageEnglish
Pages (from-to)87-93
Number of pages7
JournalHematological Oncology
Volume35
Issue number1
DOIs
Publication statusPublished - 01-03-2017

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DNA Viruses
Lymphoma, Large B-Cell, Diffuse
Viruses
Disease-Free Survival
In Situ Hybridization
RNA
Survival
Human Herpesvirus 4

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Okamoto, Akinao ; Yanada, Masamitsu ; Inaguma, Yoko ; Tokuda, Masutaka ; Morishima, Satoko ; Kanie, Tadaharu ; Yamamoto, Yukiya ; Mizuta, Shuichi ; Akatsuka, Yoshiki ; Yoshikawa, Tetsushi ; Mizoguchi, Yoshikazu ; Nakamura, Shigeo ; Okamoto, Masataka ; Emi, Nobuhiko. / The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B-cell lymphoma patients. In: Hematological Oncology. 2017 ; Vol. 35, No. 1. pp. 87-93.
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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 EBERnegative 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.",
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Okamoto, A, Yanada, M, Inaguma, Y, Tokuda, M, Morishima, S, Kanie, T, Yamamoto, Y, Mizuta, S, Akatsuka, Y, Yoshikawa, T, Mizoguchi, Y, Nakamura, S, Okamoto, M & Emi, N 2017, 'The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B-cell lymphoma patients', Hematological Oncology, vol. 35, no. 1, pp. 87-93. https://doi.org/10.1002/hon.2245

The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B-cell lymphoma patients. / Okamoto, Akinao; Yanada, Masamitsu; Inaguma, Yoko; Tokuda, Masutaka; Morishima, Satoko; Kanie, Tadaharu; Yamamoto, Yukiya; Mizuta, Shuichi; Akatsuka, Yoshiki; Yoshikawa, Tetsushi; Mizoguchi, Yoshikazu; Nakamura, Shigeo; Okamoto, Masataka; Emi, Nobuhiko.

In: Hematological Oncology, Vol. 35, No. 1, 01.03.2017, p. 87-93.

Research output: Contribution to journalArticle

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T1 - The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B-cell lymphoma patients

AU - Okamoto, Akinao

AU - Yanada, Masamitsu

AU - Inaguma, Yoko

AU - Tokuda, Masutaka

AU - Morishima, Satoko

AU - Kanie, Tadaharu

AU - Yamamoto, Yukiya

AU - Mizuta, Shuichi

AU - Akatsuka, Yoshiki

AU - Yoshikawa, Tetsushi

AU - Mizoguchi, Yoshikazu

AU - Nakamura, Shigeo

AU - Okamoto, Masataka

AU - Emi, Nobuhiko

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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 EBERnegative 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.

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