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The tumor microenvironment of classical Hodgkin lymphoma (cHL) is clearly responsible for the maintenance of the malignant Hodgkin-Reed-Sternberg (HRS) cells, and Epstein-Barr virus (EBV) has been shown to play a role in this immune evasion. EBV can increase the migration of CD4(+)CD25(+)FOXP3(+) lymphocytes, named regulatory T cells (Tregs). In this study, we assessed the distribution and biological significance of Tregs in patients with cHL. Tissue microarrays were constructed using diagnostic biopsies available in 130 cHL patients and stained with CD4, CD8, CD25, and FOXP3 antibodies. For the present study, only cHL patients whose histology could be confirmed and EBV association established were studied. From the 130 cHL patients selected for this study, 56 were classified as EBV-related and 74 EBV non-related cHL. There were no association between clinical characteristics and the expression of Tregs. However, higher levels of Tregs correlated with EBV presence on HRS cells (p = 0.02), although it did not influence event-free survival (EFS) and overall survival (p = 0.98 and p = 0.59, respectively). This study demonstrates that Tregs expression correlates with EBV presence in HRS cells and has no impact on survival of patients with cHL. Further studies investigating the mechanisms in which EBV recruits Tregs to the tumor microenvironment will contribute not only to our understanding on the pathogenesis of cHL but also to the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Classical Hodgkin's Lymphoma (cHL) has been frequently associated with Epstein-Barr virus (EBV), which can be found in a latent pattern in Reed-Sternberg (RS) cells. However, the impact of the presence of EBV in RS cells and its prognosis are still controversial. We analysed the presence of EBV in RS cells and its influence in the clinical evolution of patients with cHL treated in two public hospitals in the city of Sao Paulo, Brazil. MATERIALS AND METHODS: We selected 97 patients with cHL from 1994 to 2004. Patients were only included in this study if they had (1) >18 years, (2) negative HIV serology, (3) undergone similar chemotherapy protocols, (4) paraffin blocks available with enough material for systematic review and histological reclassification and for detection of EBV in RS cells by in situ hybridization and immunohistochemistry and (5) clinical, epidemiological and laboratorial parameters available after a thorough chart review. RESULTS: EBV was identified in 52.5% of the cases. Mixed cellularity (MC) subtype was more common in EBV-related tumours (25.5%) (p = 0.005). There was no difference on age, gender, stage and the presence of B symptoms between the two groups. The presence of EBV did not influence event free survival (EFS) (p = 0.38) or overall survival (OS) (p = 0.80) with a median follow-up of 80 months. CONCLUSION: We demonstrate that the prevalence of EBV-related cHL in this Brazilian population is 52.5% and, that, the presence of EBV does not change the clinical evolution and OS of patients treated with similar chemotherapy protocols. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]