PLoS ONE (Jan 2016)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0156384
Journal volume & issue
Vol. 11, no. 6
p. e0156384

Abstract

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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.