In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas.
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.
Department of Pathology, Paris Descartes University, AP-HP, Sorbonne Paris Cité, Hôpital Necker, Paris, France.
Danielle
D
Canioni
Department of Hematology and Drug Development, Gustave Roussy Institute, Villejuif, F-94805, France.
Jean-Marie
JM
Michot
Institut Pierre Louis d'Epidémiologie et de Santé Publique INSERM UMR S1136, Paris 6 Pierre et Marie Curie University, Paris, France.
Pascaline
P
Rabiega
Department of Pathology, Paris Descartes University, AP-HP, Sorbonne Paris Cité, Hôpital Necker, Paris, France.
Thierry J
TJ
Molina
Department of Pathology, HôpitalPitié-Salpétrière, Paris 6 Pierre et Marie Curie University, Paris, France.
Frédéric
F
Charlotte
Department of Pathology, Paris 11 Sud University, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
Thierry
T
Lazure
Department of Biological Hematology, Paris 6 Pierre et Marie Curie University, AP-HP, Hôpital Pitié-Salpétrière, Paris, France.
Frédéric
F
Davi
Department of Biological Hematology, Paris 6 Pierre et Marie Curie University, AP-HP, Hôpital Pitié-Salpétrière, Paris, France.
Catherine
C
Settegrana
Department of Pathology, Hopital Lyon Sud, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Lyon, France.
Françoise
F
Berger
Department of Internal Medicine and Digestive Diseases, Toulouse 3 University, UMR 152 IRD, Hôpital Purpan, Toulouse, France.
Laurent
L
Alric
Department of Internal Medicine, APHP, Hôpital Pitié-Salpétrière, Paris 6 Pierre et Marie Curie University, UMR 7211, INSERM, UMR S 959, CNRS, Paris, France.
Patrice
P
Cacoub
Department of Internal Medicine, APHP, Hôpital Pitié-Salpétrière, Paris 6 Pierre et Marie Curie University, UMR 7211, INSERM, UMR S 959, CNRS, Paris, France.
Benjamin
B
Terrier
Department of Adult Hematology, Paris 5 Descartes University, AP-HP, Hôpital Necker, Paris, France.|Imagine Institute, University Sorbonne Paris Cité, INSERM U 1163, CNRS ERL 8254, Paris, France.
Felipe
F
Suarez
Department of Adult Hematology, Paris 5 Descartes University, AP-HP, Hôpital Necker, Paris, France.|Imagine Institute, University Sorbonne Paris Cité, INSERM U 1163, CNRS ERL 8254, Paris, France.
David
D
Sibon
Department of Lymphoid Malignancies and Clinical Hematology, Paris 12 Est Créteil University, AP-HP, Hôpital Henri-Mondor, Créteil, France.
Jehan
J
Dupuis
Department of Hepatology, Nantes University, Hôpital de Nantes, Nantes, France.
Cyrille
C
Feray
Department of Hematology, Rouen University, Centre Henri Becquerel, Rouen, France.
Hervé
H
Tilly
Department of Hepatology, Paris 5 Descartes University, INSERM U-1016, AP-HP, Hôpital Cochin, Paris, France.
Stanislas
S
Pol
Department of Hematology, Paris Descartes University, AP-HP, Hôpital Cochin, Paris, France.
Bénédicte
B
Deau Fischer
Centre d'Immunologie de Marseille Luminy, Aix-Marseille Université INSERM U1104 CNRS UMR7280, Marseille, France.
Sandrine
S
Roulland
Department of Hemato-oncology, University Paris Sorbonne P7, INSERM U728, AP-HP, Hôpital Saint-Louis, Paris, France.
Catherine
C
Thieblemont
Department of Clinical Hematology, Paris 6 Pierre et Marie Curie, Paris, France.
Véronique
V
Leblond
Institut Pierre Louis d'Epidémiologie et de Santé Publique INSERM UMR S1136, Paris 6 Pierre et Marie Curie University, Paris, France.
Fabrice
F
Carrat
Department of Adult Hematology, Paris 5 Descartes University, AP-HP, Hôpital Necker, Paris, France.|Imagine Institute, University Sorbonne Paris Cité, INSERM U 1163, CNRS ERL 8254, Paris, France.
Olivier
O
Hermine
Department of Internal Medicine & Clinical Immunology Biological Immunology and Hematology, Paris 11 Sud University, AP-HP, Hôpital Bicêtre, INSERM U 1184, Le Kremlin-Bicêtre, France.
Caroline
C
Besson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D005260:Female; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000150:complications* / Q000821:virology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
D017361:Viral Nonstructural Proteins