title: CD40 upregulation is independent of HHV-8 in the pathogenesis of Kaposi's sarcoma.
abstract: OBJECTIVE
  Human herpesvirus 8 (HHV-8) is now acknowledged as the infective cofactor in the pathogenesis of Kaposi's sarcoma. The mode by which HHV-8 causes Kaposi's sarcoma is unresolved and it is probable that it acts in conjunction with other factors including cytokines, anti-apoptosis proteins, and cell surface receptors. CD40, a cell membrane receptor belonging to the tumour necrosis factor receptor super family, promotes B cell survival and is expressed constitutively on endothelial cells. It is upregulated on cytokine treatment and has been documented recently in Kaposi's sarcoma. Because the HHV-8 genome contains cytokine homologues, this study investigated whether CD40 expression in Kaposi's sarcoma correlated with HHV-8 status, using a unique set of HHV-8 positive and negative specimens.
  
  
  METHODS
  Twenty one paraffin wax embedded samples of Kaposi's sarcoma were selected, of which 18 were screened for the presence of HHV-8 using both conventional solution phase and TaqMan polymerase chain reaction (PCR). CD40 immunohistochemistry was assessed using a biotinylated amplification system. Staining was scored semiquantitatively.
  
  
  RESULTS
  The results indicated that the expression of CD40 is independent of viral status, being present in both HHV-8 positive and negative specimens.
  
  
  CONCLUSIONS
  This suggests that HHV-8 promotes Kaposi's sarcoma cell survival following infection by mechanisms other than those involving CD40.
authors.affiliation: Nuffield Department of Pathology and Bacteriology, University of Oxford, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Kennedy
authors.forename: S
authors.initials: S
authors.lastname: Biddolph
authors.forename: S B
authors.initials: SB
authors.lastname: Lucas
authors.forename: D D
authors.initials: DD
authors.lastname: Howells
authors.forename: S
authors.initials: S
authors.lastname: Picton
authors.forename: J O
authors.initials: JO
authors.lastname: McGee
authors.forename: J J
authors.initials: JJ
authors.lastname: O'Leary
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D005260:Female; D019288:Herpesvirus 8, Human / Q000302:isolation & purification*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D016133:Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000276:immunology* / Q000821:virology; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D019013:CD40 Antigens