PMID- 34960792 OWN - NLM STAT- MEDLINE DCOM- 20220214 LR - 20220214 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 13 IP - 12 DP - 2021 Dec 15 TI - Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein-Barr Virus in Classical Hodgkin Lymphoma. LID - 10.3390/v13122523 [doi] LID - 2523 AB - The 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. FAU - Santisteban-Espejo, Antonio AU - Santisteban-Espejo A AD - Department of Pathology, Puerta del Mar University Hospital, 11009 Cadiz, Spain. AD - Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), 11009 Cadiz, Spain. AD - Department of Medicine, Faculty of Medicine, University of Cadiz, 11003 Cadiz, Spain. FAU - Perez-Requena, Jose AU - Perez-Requena J AD - Department of Pathology, Puerta del Mar University Hospital, 11009 Cadiz, Spain. FAU - Atienza-Cuevas, Lidia AU - Atienza-Cuevas L AUID- ORCID: 0000-0002-7349-8802 AD - Department of Pathology, Puerta del Mar University Hospital, 11009 Cadiz, Spain. FAU - Moran-Sanchez, Julia AU - Moran-Sanchez J AD - Department of Medicine, Faculty of Medicine, University of Cadiz, 11003 Cadiz, Spain. AD - Department of Hematology and Hemotherapy, Puerta del Mar University Hospital, 11009 Cadiz, Spain. FAU - Fernandez-Valle, Maria Del Carmen AU - Fernandez-Valle MDC AD - Department of Hematology and Hemotherapy, Puerta del Mar University Hospital, 11009 Cadiz, Spain. FAU - Bernal-Florindo, Irene AU - Bernal-Florindo I AD - Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), 11009 Cadiz, Spain. FAU - Romero-Garcia, Raquel AU - Romero-Garcia R AUID- ORCID: 0000-0001-9851-0487 AD - Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), 11009 Cadiz, Spain. FAU - Garcia-Rojo, Marcial AU - Garcia-Rojo M AUID- ORCID: 0000-0001-6272-9401 AD - Department of Pathology, Puerta del Mar University Hospital, 11009 Cadiz, Spain. AD - Institute of Research and Innovation in Biomedical Sciences of the Province of Cadiz (INiBICA), 11009 Cadiz, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211215 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Membrane Proteins) RN - 11056-06-7 (Bleomycin) RN - 5V9KLZ54CY (Vinblastine) RN - 7GR28W0FJI (Dacarbazine) RN - 80168379AG (Doxorubicin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Bleomycin/pharmacology MH - Dacarbazine/metabolism MH - Doxorubicin/pharmacology MH - Epstein-Barr Virus Infections/*metabolism/pathology/*virology MH - Female MH - *Herpesvirus 4, Human/drug effects MH - Hodgkin Disease/drug therapy/*metabolism/pathology/*virology MH - Humans MH - Male MH - Membrane Proteins/*metabolism MH - Middle Aged MH - Prognosis MH - Reed-Sternberg Cells/metabolism MH - Survival Analysis MH - Vinblastine/pharmacology MH - Young Adult PMC - PMC8706848 OTO - NOTNLM OT - B-cell lymphomas OT - Epstein-Barr virus OT - Latent-Membrane Protein 1 OT - classical Hodgkin lymphoma OT - risk-adjusted therapy COIS- The authors declare no conflict of interest. EDAT- 2021/12/29 06:00 MHDA- 2022/02/15 06:00 PMCR- 2021/12/15 CRDT- 2021/12/28 01:07 PHST- 2021/11/18 00:00 [received] PHST- 2021/12/12 00:00 [revised] PHST- 2021/12/13 00:00 [accepted] PHST- 2021/12/28 01:07 [entrez] PHST- 2021/12/29 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] PHST- 2021/12/15 00:00 [pmc-release] AID - v13122523 [pii] AID - viruses-13-02523 [pii] AID - 10.3390/v13122523 [doi] PST - epublish SO - Viruses. 2021 Dec 15;13(12):2523. doi: 10.3390/v13122523.