title: Epstein-Barr virus-latent membrane protein 1 expression has a favorable influence in the outcome of patients with Hodgkin's Disease treated with chemotherapy.
abstract: The effect of molecular factors in the outcome of Hodgkin's Disease (HD) is being currently studied. In a previous series of HD, including patients treated only with radiotherapy and patients treated with chemotherapy (with or without radiotherapy), we found that a high proliferation index had an adverse influence in overall survival (OS) and in the achievement of a complete remission (CR). Loss of Rb expression also had an adverse prognostic influence in achievement of CR. On the other hand LMP1-EBV expression had a favorable influence for OS. The expression of other molecular factors, p53, bcl2 and CD15 did not show prognostic influence. In the present paper we have studied the effect of these molecular variables in 110 patients, of the previous series who had been treated with chemotherapy. A retrospective study was performed in these 110 patients with HD treated with chemotherapy (ABVD or variants, 62%, or regimes not containing adriamycin, 38%) with or without adjutant radiotherapy, collected at the 11 centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. The prognostic value of clinical variables and the expression of p53, bcl2, CD15, Rb, LMP 1-EBV and proliferative fraction demonstrated with sensitive immunohistochemical methods were studied. Cox's multivariate analysis was performed to assess their influence in failure-free survival (FFS) and OS. A multivariate logistic regression analysis was performed for studying the effect of the variables in the achievement of a CR. Of the clinical variables, only advanced stage (III/IV) had a significant independent adverse influence in FFS, in OS and in the achievement of CR and advanced age in OS. Of the molecular variables, LMP1-EBV had an independent and strong favorable influence in FFS, in OS and in the achievement of CR. Rb expression had a modest favorable influence in CR. The rest of the molecular variables had no independent influence on the outcome of the disease. In conclusion these results confirm the favorable prognostic value of LMP1-EBV expression in the subset of patients with HD treated with chemotherapy.
authors.affiliation: Department of Internal Medicine, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain. cmontalban@hrc.insalud.es
authors.forename: C
authors.initials: C
authors.lastname: Montalban
authors.forename: V
authors.initials: V
authors.lastname: Abraira
authors.forename: M
authors.initials: M
authors.lastname: Morente
authors.forename: A
authors.initials: A
authors.lastname: Acevedo
authors.forename: B
authors.initials: B
authors.lastname: Aguilera
authors.forename: C
authors.initials: C
authors.lastname: Bellas
authors.forename: M
authors.initials: M
authors.lastname: Fraga
authors.forename: R G
authors.initials: RG
authors.lastname: Del Moral
authors.forename: J
authors.initials: J
authors.lastname: Menarguez
authors.forename: H
authors.initials: H
authors.lastname: Oliva
authors.forename: M
authors.initials: M
authors.lastname: Sanchez-Beato
authors.forename: M A
authors.initials: MA
authors.lastname: Piris
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D005629:Frozen Sections; D006689:Hodgkin Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D013534:Survival; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016160:Retinoblastoma Protein; D014763:Viral Matrix Proteins