Quantification of Epstein-Barr Virus (EBV)-DNA in Peripheral Blood as Biomarker in Hodgkin Lymphoma.
Luigi M Larocca, Stefan Hohaus, Tonia Cenci, Maurizio Martini, Giuseppe Leone. Catholic University, School of Medicine, Rome, Italy
Background: The Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of 20-40% cases of Hodgkin lymphoma (HL) in western countries. We evaluated the detection and quantification of cell-free plasma EBV-DNA as biomarker in HL.
Design: The presence of EBV in peripheral blood compartments (whole blood, plasma, and mononuclear cells) at diagnosis was analyzed using real-time PCR for the EBNA region (n=93) and in HRS cells using in-situ hybridization for EBER (n=63). These data were correlated to histological and clinical characteristics, EBV serology, and other circulating biomarkers.
Results: The presence of EBV-DNA in whole blood had the highest sensitivity to detect EBV-associated HL (78.6%), while the detection of EBV-DNA in plasma had the highest specificity (89.7%). EBER-positivity was associated with age over 50 years, histological subtype other than type 1 nodular sclerosis, over 5% tumor-associated CD68+ macrophages in lymph node biopsies and low EBNA-1 antibody titers. In EBV-associated HL, plasma EBV-DNA copy numbers were higher in patients older than 50 years, with over 5% CD68+ cells, advanced stage disease, presence of B-symptoms, and IPS score >2. Plasma EBV-DNA load correlated to the circulating cell-free DNA and IL-6 levels, and was inversely correlated to lymphocyte counts and EBNA1 titers. It was also associated with inferior progression-free survival.
Conclusions: Quantification of EBV-DNA in peripheral blood at diagnosis is a reliable marker of EBV-associated HL. It is also an indicator of disease activity and is associated to unfavourable outcome. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immune surveillance, favouring the expansion of EBV-HRS cells in HL.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 152, Tuesday Afternoon