mTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma

Human Pathology
Darcy A KerrRosalynn M Nazarian

Abstract

Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates, and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (N=274), most (90%) associated with human immunodeficiency virus. Tissue microarray slides were stained with human herpes virus-8, Friend leukemia integration 1 transcription factor, CD117 (c-kit), phospho-S6 (pS6), PDGF receptor-β, VEGF, and phospho-mTOR. Both intensity and extent of staining were scored. Multiplying these scores for each core yielded total staining H-scores. Human herpes virus-8 was positive in 87% and Friend leukemia integration 1 transcription factor in 95.7% of cases. Most were also VEGF+ (97.6%), pS6+ (95.7%), CD117+ (92.5%), and PDGFRB+ (87.4%). Approximately half (55.6%) were phospho-mTOR+. There was no significant difference in staining among patients with low (<500 cells...Continue Reading

Citations

Jul 16, 2019·The Journal of Clinical Investigation·Tingting LiShou-Jiang Gao
Nov 20, 2019·Ophthalmic Plastic and Reconstructive Surgery·Jan P Ulloa-PadillaDarcy A Kerr
May 2, 2020·Cells·Burkitkan AkbaySvetlana Dokudovskaya
Oct 30, 2019·Open Forum Infectious Diseases·Sanni J RinneMervi Aavikko
Aug 24, 2017·Clinical Transplantation·Gérôme BohelayUNKNOWN Skin and Organ Transplantation Group of the French Society of Dermatology
Mar 25, 2020·Blood·Daniel J ArenasDavid C Fajgenbaum

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