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]
Overview
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 saliva via close sexual contact.
- Another minor route of transmission for HHV8 is through organ transplantation.
- 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
- 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 inflamation surrounding the tumor which leads to mild painful swelling of the area