In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas.
oleh: Danielle Canioni, Jean-Marie Michot, Pascaline Rabiega, Thierry J Molina, Frédéric Charlotte, Thierry Lazure, Frédéric Davi, Catherine Settegrana, Françoise Berger, Laurent Alric, Patrice Cacoub, Benjamin Terrier, Felipe Suarez, David Sibon, Jehan Dupuis, Cyrille Feray, Hervé Tilly, Stanislas Pol, Bénédicte Deau Fischer, Sandrine Roulland, Catherine Thieblemont, Véronique Leblond, Fabrice Carrat, Olivier Hermine, Caroline Besson, national ANRS HC13 LymphoC study
| Format: | Article |
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| Diterbitkan: | Public Library of Science (PLoS) 2016-01-01 |
Deskripsi
Hepatitis C Virus (HCV) infection is associated with the B-cell non-Hodgkin lymphomas (NHL), preferentially marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL). While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL), a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3) protein. Lympho-C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36%) and MZL (34%). Almost half of DLBCL (12/26) were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%). There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006). Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas.