Expressão do vírus Epstein-Barr em células tumorais do Linfoma de Hodgkin Clássico: correlação com fatores desfavoráveis e sobrevida

Abstract

Introduction: The association between classical Hodgkin’s Lymphoma and tumor Epstein-Barr virus status is well established. However, the expression of Epstein-Barr virus presence in Hodgkin/Reed-Sternberg cells and its prognosis remains controversial and presentes conflicting results in studies worldwide. Understanding the pathophysiological role of this virus in the prognosis of patients with classical Hodgkin’s Lymphoma is essential. Objective: The aim of this study is to correlate the clinical outcome with Epstein-Barr virus status in a Brazilian population. Methods: Epstein-Barr virus positivity was determined by in situ hybridization for Epstein-Barr virus-encoded ribonucleic acid and immunohistochemistry for viral latent membrane protein-1. The histopathology review and the analysis of identification tests were performed by an hematopathologist expert. The prognostic impact of Epstein-Barr virus status in 29 patients with classical Hodgkin’s Lymphoma was evaluated. Prognostic factors from International Prognostic Score to advanced stage and risk factors from German Hodgkin Study Group to limited stage were correlated with tumor cells Epstein-Barr virus status. In order to determine associations between the presence of Epstein-Barr virus and other categorical variables, Chi-square or Fisher's exact tests were applied. Overall and event-free survivals were analyzed with Kaplan-Meier method and Cox proportional hazards regression models. Results: The mean age at diagnosis was 33 years. Tumor cells Epstein-Barr virus status was positive in 37.9%. Epstein-Barr virus-positive classical Hodgkin’s Lymphoma was more frequent in patients older than 45 years, with no statistical difference. Mixed cellularity histological subtype was more common in Epstein-Barr virus-related tumor cells (p = 0.02) and its effect-size index was medium. Univariate analysis, event-free survival and overall survival were not significantly associated to age, sex, clinical stage, hemoglobin, leukocytes, lymphocytes, albumin, nodal involvement, B symptoms, extranodal disease and Bulky disease in Epstein-Barr virus-positive and negative patients (p > 0.05). Epstein-Barr virus-positive patients had longer event free survival when compared to Epstein-Barr virus-negative ones, even though the difference was not statistically significant (p = 0.07). In multivariate analysis, Epstein Barr virus positivity was not a significant prognostic factor. Conclusions: Although the Epstein-Barr virus status in tumor cells was not associated with adverse prognostic factors and did not influence the overall and event-free survivals, a positive association between the presence of Epstein-Barr virus and Mixed-cellularity subtype was noticed.