Journal Article

In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas

Dupuis, Jehan, Tilly, Hervé, Davi, Frédéric, Charlotte, Frédéric, Deau Fischer, Bénédicte, Hermine, Olivier, Alric, Laurent, Cacoub, Patrice, Suarez, Felipe, Feray, Cyrille, Rabiega, Pascaline, Settegrana, Catherine, Besson, Caroline, Canioni, Danielle, Carrat, Fabrice, Berger, Françoise, Thieblemont, Catherine, Roulland, Sandrine, Lazure, Thierry, Pol, Stanislas, Leblond, Véronique, Michot, Jean-Marie, Molina, Thierry J., Terrier, Benjamin, Sibon, David

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Aged, 80 and over / Antigens / B cells / B-cell lymphoma / B-Lymphocytes - metabolism / B-Lymphocytes - virology / Biology and Life Sciences / Care and treatment / Complications and side effects / Deoxyribonucleic acid / DNA / DNA repair / Female / Health aspects / Hematology / Hepacivirus - metabolism / Hepatitis / Hepatitis C / Hepatitis C - complications / Hepatitis C - virology / Hepatitis C virus / Hepatology / Humans / Immunology / Infections / Influence / Internal medicine / Life Sciences / Lymphocytes B / Lymphoma / Lymphoma, B-Cell - etiology / Lymphoma, B-Cell - virology / Male / Medicine / Medicine and Health Sciences / Middle Aged / Non-Hodgkin's lymphomas / NS3 protein / Observational studies / Pathology / Proteins / Research and Analysis Methods / Risk factors / Sibon / Transformation / Viral Nonstructural Proteins - genetics / Viral Nonstructural Proteins - metabolism / Viruses