Kaposi's sarcoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]

Pathogenesis

• Kaposi's sarcoma arises from endothelial cells, which are epithelial cells that normally lines the interior surface of blood vessels and lymphatic vessels.
• Kaposi's sarcoma is mainly caused by an infection with Human herpes virus 8 (HHV8), which is also known as Kaposi's sarcoma-associated herpes virus (KSHV).
• HHV8 is usually transmitted through both saliva and semen via close sexual contact.
• Another minor route of transmission for HHV8 is through organ transplantation.
• Kaposi's sarcoma is a widely disseminated disease that may involve the skin, oral cavity, gastrointestinal tract, and respiratory airways.
• Cutaneous manifestations of Kaposi's sarcoma is due to:

• The high vascularity of the tumor which leads to leakage of RBC into the surrounding tissue
• The inflammatory process which surrounds the tumor and leads to a mild painful swelling of the area

Genetics

• The oncogenesis of HHV8 infection is due to a number of human cellular genes that have been incorporated through molecular piracy into the viral DNA sequence.
• The genes acquired by HHV8 will augment the cellular proliferation pathways of infected cells through various mediators and DNA synthesis proteins such as:

• Complement-binding protein
• IL-6
• BCL-2
• Cyclin-D
• Interferon regulatory factor
• Flice inhibitory protein (FLIP)
• Dihydrofolate reductase
• Thymidine kinase
• Thymidylate synthetase
• DNA polymerase

• The augmentation of cellular pathways will protect the virus from the immune system and allow a continuous viral replication during the latency period.
• During the latent period, HHV8 will express a viral latency-associated nuclear antigen (LANA) that acts as:

• A tethering molecule that stabilize the viral DNA to the cellular chromosome
• An inhibitor of p53 tumor suppressor protein
• An inhibitor of retinoblastoma (Rb) tumor suppressor protein
• A suppressor of the viral lytic phase of replication

References

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