title: Lack of HCV infection in malignant cells refutes the hypothesis of a direct transforming action of the virus in the pathogenesis of HCV-associated B-cell NHLs.
abstract: OBJECTIVE
  Preliminary evidence suggests that hepatitis C virus (HCV) might play a pathogenetic role in autoimmune-related, non-malignant B-cell lymphoproliferation, as well as in a subset of B-cell non-Hodgkin's lymphomas (NHLs). With regard to the mechanism(s) by which HCV might favor B-cell expansion and malignant transformation, most data support an indirect pathogenetic role of the virus as an exogenous trigger. A direct oncogenetic role of HCV by direct cell infection and deregulation has only been hypothesized on the basis of the lymphotropism of the virus.
  
  
  METHODS
  In this study we investigated the possible HCV infection of NHL B cells by means of sensitive and quantitative polymerase chain reaction (PCR) on affinity-purified neoplastic cells, and by HCV-specific immunohistochemistry and in situ hybridization.
  
  
  RESULTS
  HCV infection of neoplastic B cells was documented in only three cases, namely the low-grade B-cell NHLs that arose in the course of mixed cryoglobulinemia syndrome (MC). HCV infection, below one viral genome per cell, was detectable only by PCR. All the remaining low-grade (one case) and high-grade B-cell NHLs (two cases) were HCV uninfected. Previous immunoglobulin gene analyses were consistent with an antigen-driven B-cell lymphoproliferation in the studied cases.
  
  
  CONCLUSIONS
  Overall, our data are consistent with an indirect oncogenetic role of HCV in B-cell lymphomagenesis as an exogenous trigger. Infection of B cells by HCV appears possible in some NHL subsets, but the implications remain unknown.
authors.affiliation: Division of Rheumatology, DPMSC, University of Udine, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Vita
authors.forename: Valli
authors.initials: V
authors.lastname: De Re
authors.forename: Domenico
authors.initials: D
authors.lastname: Sansonno
authors.forename: Annunziata
authors.initials: A
authors.lastname: Gloghini
authors.forename: Daniela
authors.initials: D
authors.lastname: Gasparotto
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
authors.forename: Stefania
authors.initials: S
authors.lastname: Sacco
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
authors.forename: Mauro
authors.initials: M
authors.lastname: Boiocchi
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology* / Q000821:virology*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D016393:Lymphoma, B-Cell / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000302:isolation & purification
chemical_list: D012367:RNA, Viral