{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:47:46Z","timestamp":1773157666607,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018780","name":"Andalusian Health Service","doi-asserted-by":"publisher","award":["RH-0145-2020"],"award-info":[{"award-number":["RH-0145-2020"]}],"id":[{"id":"10.13039\/501100018780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI-0032-2017"],"award-info":[{"award-number":["PI-0032-2017"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The prognostic impact of the presence of Epstein\u2013Barr 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\u2013Reed\u2013Sternberg (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\u2013Meier 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 &lt; 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\u20130.48, p = 0.004) and limited disease stages (I\u2013II) (HR: 0.074, 95% CI: 0.01\u20130.47, 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\u20130.57, 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.<\/jats:p>","DOI":"10.3390\/v13122523","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T21:47:36Z","timestamp":1639604856000},"page":"2523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein\u2013Barr Virus in Classical Hodgkin Lymphoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Antonio","family":"Santisteban-Espejo","sequence":"first","affiliation":[{"name":"Department of Pathology, Puerta del Mar University Hospital, 11009 Cadiz, Spain"},{"name":"Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), 11009 Cadiz, Spain"},{"name":"Department of Medicine, Faculty of Medicine, University of Cadiz, 11003 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose","family":"Perez-Requena","sequence":"additional","affiliation":[{"name":"Department of Pathology, Puerta del Mar University Hospital, 11009 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7349-8802","authenticated-orcid":false,"given":"Lidia","family":"Atienza-Cuevas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Puerta del Mar University Hospital, 11009 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Moran-Sanchez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, University of Cadiz, 11003 Cadiz, Spain"},{"name":"Department of Hematology and Hemotherapy, Puerta del Mar University Hospital, 11009 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Fernandez-Valle","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hemotherapy, Puerta del Mar University Hospital, 11009 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Bernal-Florindo","sequence":"additional","affiliation":[{"name":"Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), 11009 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9851-0487","authenticated-orcid":false,"given":"Raquel","family":"Romero-Garcia","sequence":"additional","affiliation":[{"name":"Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), 11009 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6272-9401","authenticated-orcid":false,"given":"Marcial","family":"Garcia-Rojo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Puerta del Mar University Hospital, 11009 Cadiz, Spain"},{"name":"Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), 11009 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41375-021-01204-6","article-title":"Molecular biology of Hodgkin lymphoma","volume":"35","author":"Weniger","year":"2021","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/hon.723","article-title":"Epidemiology of Hodgkin\u2019s disease: A review","volume":"22","author":"Cartwright","year":"2004","journal-title":"Hematol. 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