Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma.
Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.
Dupin
N
N
Departments of Oncology and Molecular Pathology, Royal Free and University College Medical School, UCL, London, United Kingdom W1P 6BT.
Fisher
C
C
Kellam
P
P
Ariad
S
S
Tulliez
M
M
Franck
N
N
van Marck
E
E
Salmon
D
D
Gorin
I
I
Escande
J P
JP
Weiss
R A
RA
Alitalo
K
K
Boshoff
C
C
D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology / Q000821:virology; D005871:Castleman Disease / Q000473:pathology / Q000821:virology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000302:isolation & purification* / Q000502:physiology*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D008223:Lymphoma / Q000473:pathology / Q000821:virology*; D009101:Multiple Myeloma / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D040321:Vascular Endothelial Growth Factor Receptor-3; D017735:Virus Latency
D015703:Antigens, CD; D015415:Biomarkers; D011956:Receptors, Cell Surface; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3