Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein-Barr Virus in Classical Hodgkin Lymphoma

dc.contributor.authorSantisteban-Espejo, Antonio
dc.contributor.authorPerez-Requena, Jose
dc.contributor.authorAtienza-Cuevas, Lidia
dc.contributor.authorMoran-Sanchez, Julia
dc.contributor.authordel Carmen Fernandez-Valle, Maria
dc.contributor.authorBernal-Florindo, Irene
dc.contributor.authorRomero-Garcia, Raquel
dc.contributor.authorGarcia-Rojo, Marcial
dc.contributor.authoraffiliation[Santisteban-Espejo, Antonio] Puerta Mar Univ Hosp, Dept Pathol, Cadiz 11009, Spain
dc.contributor.authoraffiliation[Perez-Requena, Jose] Puerta Mar Univ Hosp, Dept Pathol, Cadiz 11009, Spain
dc.contributor.authoraffiliation[Atienza-Cuevas, Lidia] Puerta Mar Univ Hosp, Dept Pathol, Cadiz 11009, Spain
dc.contributor.authoraffiliation[Garcia-Rojo, Marcial] Puerta Mar Univ Hosp, Dept Pathol, Cadiz 11009, Spain
dc.contributor.authoraffiliation[Santisteban-Espejo, Antonio] Prov Cadiz INiBICA, Inst Res & Innovat Biomed Sci, Cadiz 11009, Spain
dc.contributor.authoraffiliation[Bernal-Florindo, Irene] Prov Cadiz INiBICA, Inst Res & Innovat Biomed Sci, Cadiz 11009, Spain
dc.contributor.authoraffiliation[Romero-Garcia, Raquel] Prov Cadiz INiBICA, Inst Res & Innovat Biomed Sci, Cadiz 11009, Spain
dc.contributor.authoraffiliation[Garcia-Rojo, Marcial] Prov Cadiz INiBICA, Inst Res & Innovat Biomed Sci, Cadiz 11009, Spain
dc.contributor.authoraffiliation[Santisteban-Espejo, Antonio] Univ Cadiz, Dept Med, Fac Med, Cadiz 11003, Spain
dc.contributor.authoraffiliation[Moran-Sanchez, Julia] Univ Cadiz, Dept Med, Fac Med, Cadiz 11003, Spain
dc.contributor.authoraffiliation[Moran-Sanchez, Julia] Puerta del Mar Univ Hosp, Dept Hematol & Hemotherapy, Cadiz 11009, Spain
dc.contributor.authoraffiliation[del Carmen Fernandez-Valle, Maria] Puerta del Mar Univ Hosp, Dept Hematol & Hemotherapy, Cadiz 11009, Spain
dc.contributor.funderAndalusia Health System and with the EU FEDER ITI Grant for Cadiz Province
dc.contributor.funderPostdoctoral grant from the Andalusia Health System
dc.contributor.funderEU FEDER ITI Grant for Cadiz Province
dc.date.accessioned2025-01-07T13:07:38Z
dc.date.available2025-01-07T13:07:38Z
dc.date.issued2021-12-15
dc.description.abstractThe prognostic impact of the presence of Epstein-Barr virus (EBV) in classical Hodgkin lymphoma (cHL) is controversial. Previous studies reported heterogeneous results, rendering difficult the clinical validation of EBV as a prognostic biomarker in this lymphoma. The objective of this study was to evaluate the survival impact of the expression of EBV Latent-Membrane Protein 1 (EBV-LMP1) in tumoral Hodgkin-Reed-Sternberg (HRS) cells of primary diagnostic samples of cHL. Formalin-Fixed Paraffin-Embedded (FFPE) lymph node samples from 88 patients with cHL were analyzed. Patients were treated with the standard first-line chemotherapy (CT) with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) followed by radiotherapy. The Kaplan-Meier method and the Cox proportional hazards model were used for carrying out the survival analysis. In order to investigate whether the influence of EBV was age-dependent, analyses were performed both for patients of all ages and for age-stratified subgroups. In bivariate analysis, the expression of EBV was associated with older age (p = 0.011), mixed cellularity subtype cHL (p < 0.001) and high risk International Prognostic Score (IPS) (p = 0.023). Overall survival (OS) and progression-free survival (PFS) were associated with the presence of bulky disease (p = 0.009) and advanced disease at diagnosis (p = 0.016). EBV-positive cases did not present a significantly lower OS and PFS in comparison with EBV-negative cases, for all ages and when stratifying for age. When adjusted for covariates, absence of bulky disease at diagnosis (HR: 0.102, 95% CI: 0.02-0.48, p = 0.004) and limited disease stages (I-II) (HR: 0.074, 95% CI: 0.01-0.47, p = 0.006) were associated with a significant better OS. For PFS, limited-disease stages also retained prognostic impact in the multivariate Cox regression (HR: 0.145, 95% CI: 0.04-0.57, p = 0.006). These results are of importance as the early identification of prognostic biomarkers in cHL is critical for guiding and personalizing therapeutic decisions. The prognostic role of EBV in cHL could be modulated by the type of CT protocol employed and interact with the rest of presenting features.
dc.description.sponsorshipThis work has been supported by a postdoctoral grant (RH-0145-2020) from the Andalusia Health System and with the EU FEDER ITI Grant for Cadiz Province PI-0032-2017.
dc.description.version
dc.identifier.citationSantisteban-Espejo A, Perez-Requena J, Atienza-Cuevas L, Moran-Sanchez J, del Carmen Fernandez-Valle M, Bernal-Florindo I, et al. Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein-Barr Virus in Classical Hodgkin Lymphoma. Viruses. 2021;13(12):2523. Published 2021 Dec 15.
dc.identifier.doi10.3390/v13122523
dc.identifier.essn1999-4915
dc.identifier.issn1999-4915
dc.identifier.pmcPMC8706848
dc.identifier.pmid34960792
dc.identifier.unpaywallURLhttps://www.mdpi.com/1999-4915/13/12/2523/pdf?version=1639711053
dc.identifier.urihttps://hdl.handle.net/10668/25268
dc.identifier.wosID737465700001
dc.issue.number12
dc.journal.titleViruses-basel
dc.journal.titleabbreviationViruses-basel
dc.language.isoen
dc.organizationSAS - Hospital Universitario Puerta del Mar
dc.organizationInstituto de Investigación e Innovación Biomédica de Cádiz (INiBICA)
dc.page.number14
dc.provenanceRealizada la curación de contenido 20/05/2025
dc.publisherMdpi
dc.relation.projectIDRH-0145-2020
dc.relation.projectIDPI-0032-2017
dc.relation.publisherversionhttps://www.mdpi.com/1999-4915/13/12/2523
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectB-cell lymphomas
dc.subjectclassical Hodgkin lymphoma
dc.subjectEpstein-Barr virus
dc.subjectLatent-Membrane Protein 1
dc.subjectrisk-adjusted therapy
dc.subjectAge-defined subgroups
dc.subjectReed-sternberg cells
dc.subjectB-cells
dc.subjectPresenting features
dc.subjectDisease
dc.subjectImpact
dc.subjectEbv
dc.subjectInfection
dc.subjectLmp1
dc.subjectMembrane-protein-1
dc.subject.decsHerpesvirus Humano 4
dc.subject.decsEnfermedad de Hodgkin
dc.subject.decsProteínas de la Membrana
dc.subject.decsDoxorrubicina
dc.subject.decsGanglios Linfáticos
dc.subject.decsDacarbazina
dc.subject.decsFormaldehído
dc.subject.decsRadioterapia
dc.subject.decsVinblastina
dc.subject.decsQuimioterapia
dc.subject.meshHodgkin Disease
dc.subject.meshHerpesvirus 4, Human
dc.subject.meshVinblastine
dc.subject.meshBleomycin
dc.subject.meshDacarbazine
dc.subject.meshDoxorubicin
dc.subject.meshEpstein-Barr Virus Infections
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshLymphoma
dc.subject.meshTomography, X-Ray Computed
dc.titlePrognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein-Barr Virus in Classical Hodgkin Lymphoma
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number13
dc.wostypeArticle

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