Transmission of Angiosarcomas From a Common Multiorgan Donor to Four Transplant Recipients

: We describe the donor tumor transmission of metastatic angiosarcomas to four transplant recipients through transplantation of deceased-donor organs, i.e. kidneys, lung and liver, from an apparently unaffected common female multiorgan donor. Fluorescent in situ hybridization of angiosarcoma cells confirmed that the tumor was of female donor's origin in male kidney recipients. Recent literature associated increased urokinase-plasminogen-activator-receptor (uPAR) and plasma soluble urokinase-plasminogen-activator-receptor (suPAR) levels with metastatic malignancies. Now we found that, compared to baseline levels, both deceased-donor kidney recipients showed increased uPAR transcripts in mononuclear cells as well as increased plasma suPAR levels after the diagnosis of metastatic angiosarcomas, i.e. 4 months after donor tumor transmission. These results show an association of uPAR/suPAR in donor tumor transmission of metastatic angiosarcomas in humans. Copyright (C) 2013 Blackwell Publishing Ltd.; References: 1. Kauffman HM, McBride MA, Cherikh WS, Spain PC, Marks WH, Roza AM. Transplant tumor registry: Donor related malignancies. Transplantation, 2002; 74: 358-362. 2. Ahmed I, Hamacher KL. Angiosarcoma in a chronically immunosuppressed renal transplant recipient: Report of a case and review of the literature. Am J Dermatopathol, 2002; 24: 330-335. 3. Blasi F, Carmeliet P. uPAR: A versatile signaling orchestrator. Nat Rev Mol Cell Biol, 2002; 12: 932-943. 4. Riisbro R, Christensen IJ, Nielsen HJ, Brunner N, Nilbert M, Fernebro E. Preoperative plasma soluble urokinase plasminogen activator receptor as a prognostic marker in rectal cancer patients. An EORTC-Receptor and Biomarker Group collaboration. Int J Biol Markers, 2005; 20: 93-102. 5. Thomassen A, Lerberg Nielsen A, Gerke O, Johansen A, Petersen H. Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination. Eur J Nucl Med Mol Imaging, 2011; 38: 894-898. 6. Liu Y, Echtermeyer F, Thilo F, et al. The proteoglycan syndecan 4 regulates transient receptor potential canonical 6 channels via RhoA/Rho-associated protein kinase signaling. Arterioscler Thromb Vasc Biol, 2012; 32: 378-385. 7. Wuensch T, Thilo F, Krueger K, Scholze A, Ristow M, Tepel M. High glucose-induced oxidative stress increases transient receptor potential channel expression in human monocytes. Diabetes, 2010; 59: 844-849. 8. Ison MG, Hager J, Blumberg E, et al. Donor-derived disease transmission events in the United States: Data reviewed by the OPTN/UNOS Disease Transmission Advisory Committee. Am J Transplant, 2009; 9: 1929-1935. 9. Nalesnik MA, Woodle ES, Dimaio JM, et al. Donor-transmitted malignancies in organ transplantation: Assessment of clinical risk. Am J Transplant, 2011; 11: 1140-1147. 10. Zanetta L, Corada M, Grazia Lampugnani M, et al. Downregulation of vascular endothelial-cadherin expression is associated with an increase in vascular tumor growth and hemorrhagic complications. Thromb Haemost, 2005; 93: 1041-1046. 11. Khan MM, Bradford HN, Isordia-Salas I, et al. High-molecular-weight kininogen fragments stimulate the secretion of cytokines and chemokines through uPAR, Mac-1, and gC1qR in monocytes. Arterioscler Thromb Vasc Biol, 2006; 26: 2260-2266. 12. Kim MH, Yoo HS, Kim MY, et al. Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-kappaB signaling in human gastric carcinoma cells. Int J Mol Med, 2007; 19: 689-697. 13. Lee KH, Kim SW, Kim JR. Reactive oxygen species regulate urokinase plasminogen activator expression and cell invasion via mitogen-activated protein kinase pathways after treatment with hepatocyte growth factor in stomach cancer cells. J Exp Clin Cancer Res, 2009; 28: 73. 14. Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med, 2011; 364: 656-665.