Molecular Pathology, Vol 52, Issue 1 32-36, Copyright © 1999 by Journal of Clinical Pathology
CD40 upregulation is independent of HHV-8 in the pathogenesis of Kaposi's sarcoma
MM Kennedy, S Biddolph, SB Lucas, DD Howells, S Picton, JO McGee and JJ O'Leary
Nuffield Department of Pathology and Bacteriology, University of Oxford, UK.
AIMS: 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.
