Abstract
Kaposi's sarcoma (KS) is a highly and abnormally vascularized tumor-like lesion affecting the skin, lymphnodes and viscera, which develops from early inflammatory stages of patch/plaque to late, nodular tumors composed predominant of spindle cells (SC). These SC are infected with the Kaposi's sarcoma-associated herpesvirus or human herpesvirus-8 (KSHV/HHV-8). KS is promoted during HIV infection by various angiogenic and pro-inflammatory factors including HIV-Tat. The latency associated nuclear antigen type 1 (LANA-1) protein is well expressed in SC, highly immunogenic and considered important in the generation and maintenance of HHV-8 associated malignancies. Various studies favour an endothelial origin of the KS SC, expressing "mixed" lymphatic and vascular endothelial cell markers, possibly representing hybrid phenotypes of endothelial cells (EC). A significant number of SC during KS development are apparently not HHV8 infected, which heterogeneity in viral permissiveness may indicate that non-infected SC may continuously be recruited in to the lesion from progenitor cells and locally triggered to develop permissiveness to HHV8 infection. In the present study various aspects of KS pathogenesis are discussed, focusing on the histopathological as well as cytogenetic and molecular genetic changes in KS.
Highlights
Kaposi's sarcoma Kaposi's sarcoma first described by Moritz Kaposi in 1872 as "idiopathic multiple pigmented sarcomas of the skin" [1] is an angioproliferative, tumour-like lesion usually developing in the skin [2], and eventually disseminating to multiple cutaneous sites, viscera and lymph nodes
The virus was rapidly characterised as a Kaposi's sarcoma (KS) associated herpes virus (KSHV) and classified as human herpes virus type 8 (HHV-8)
LANA+/CD34-cells were more frequent in early as compared to late lesions and did not express a leucocytic phenotype (CD3, CD20, CD45, CD68) [22], but most expressed lymphatic endothelial (LEC) markers such as LYVE-1, VEGFR-3 and D2-40, suggesting that resident lymphatic endothelial cells (LEC) represent an early target of primary HHV-8 infection [23]
Summary
Kaposi's sarcoma Kaposi's sarcoma first described by Moritz Kaposi in 1872 as "idiopathic multiple pigmented sarcomas of the skin" [1] is an angioproliferative, tumour-like lesion usually developing in the skin [2], and eventually disseminating to multiple cutaneous sites, viscera and lymph nodes. LANA+/CD34-cells were more frequent in early as compared to late lesions and did not express a leucocytic phenotype (CD3, CD20, CD45, CD68) [22], but most expressed lymphatic endothelial (LEC) markers such as LYVE-1, VEGFR-3 and D2-40, suggesting that resident LECs represent an early target of primary HHV-8 infection [23] This is supported by other findings [54] that infected LECs have a higher HHV8 genome copy number than VECs. Obviously a high viral copy number may result in an efficient maintenance and propagation of episomal HHV-8 DNA in dividing and migrating LECs. in-vitro activation of VEGFR-3 by HHV-8 has been shown to increase endothelial cell migration and to enhance cell susceptibility to HHV-8 infection and transformation [43]. In summary the concept of oncogenesis related to infection is well exemplified by the herpes virus HHV-8 and retrovirus HIV-1 associated Kaposi's sarcoma, which develops due to the effects of various host-cells and viral factors elicited during infection affecting cell proliferation, cell escape from apoptosis and dysregulation of host immune responses
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