P Redondo1, T Solano, B VAzquez, A Bauza, M Idoate. 1. Department of Dermatology, University Clinic of Navarra, P.O.Box 192, 31080 Pamplona, Spain. predondo@unav.es
Abstract
BACKGROUND: The Fas/Fas ligand (FasL) system plays a key part in maintaining tissue homeostasis via the induction of apoptosis. Functional impairment of the Fas/FasL system is associated with the development and progression of malignancies. Malignant melanoma cells and tissues have been shown to express Fas and FasL to variable extents. OBJECTIVES: To demonstrate the expression and the presence of soluble circulating levels of Fas and FasL in cutaneous malignant melanoma. METHODS: Biopsy specimens of 42 patients with primary melanoma and nine patients with cutaneous metastatic melanoma were obtained for immunohistochemistry studies. All patients were followed for at least 5 years. In another 46 patients with melanoma (15 stage I and II; 11 stage III; and 20 stage IV) and in 10 healthy volunteer control subjects circulating levels of Fas and FasL were analysed with commercial ELISA tests. RESULTS: FasL was strongly positive in 38 (90%) of 42 primary melanomas; two of nine metastases did not express FasL. In the primary melanomas Fas was strongly or intensely positive in 17 (40%), moderately or weakly positive in 10 (24%) and negative in 15 (36%) of 42 melanomas. Soluble Fas plasma levels in patients with metastatic malignant melanoma were significantly elevated over those in the control group (P = 0.01). CONCLUSIONS: The absence of Fas in most of the thick melanomas that did not metastasize, and in insitu melanomas, might be taken as a theoretical factor for a good prognosis. Soluble Fas is increased in patients with metastatic melanoma and might be associated with poor prognosis.
BACKGROUND: The Fas/Fas ligand (FasL) system plays a key part in maintaining tissue homeostasis via the induction of apoptosis. Functional impairment of the Fas/FasL system is associated with the development and progression of malignancies. Malignant melanoma cells and tissues have been shown to express Fas and FasL to variable extents. OBJECTIVES: To demonstrate the expression and the presence of soluble circulating levels of Fas and FasL in cutaneous malignant melanoma. METHODS: Biopsy specimens of 42 patients with primary melanoma and nine patients with cutaneous metastatic melanoma were obtained for immunohistochemistry studies. All patients were followed for at least 5 years. In another 46 patients with melanoma (15 stage I and II; 11 stage III; and 20 stage IV) and in 10 healthy volunteer control subjects circulating levels of Fas and FasL were analysed with commercial ELISA tests. RESULTS:FasL was strongly positive in 38 (90%) of 42 primary melanomas; two of nine metastases did not express FasL. In the primary melanomas Fas was strongly or intensely positive in 17 (40%), moderately or weakly positive in 10 (24%) and negative in 15 (36%) of 42 melanomas. Soluble Fas plasma levels in patients with metastatic malignant melanoma were significantly elevated over those in the control group (P = 0.01). CONCLUSIONS: The absence of Fas in most of the thick melanomas that did not metastasize, and in insitu melanomas, might be taken as a theoretical factor for a good prognosis. Soluble Fas is increased in patients with metastatic melanoma and might be associated with poor prognosis.
Authors: N Jacquelot; M P Roberti; D P Enot; S Rusakiewicz; N Ternès; S Jegou; D M Woods; A L Sodré; M Hansen; Y Meirow; M Sade-Feldman; A Burra; S S Kwek; C Flament; M Messaoudene; C P M Duong; L Chen; B S Kwon; A C Anderson; V K Kuchroo; B Weide; F Aubin; C Borg; S Dalle; O Beatrix; M Ayyoub; B Balme; G Tomasic; A M Di Giacomo; M Maio; D Schadendorf; I Melero; B Dréno; A Khammari; R Dummer; M Levesque; Y Koguchi; L Fong; M Lotem; M Baniyash; H Schmidt; I M Svane; G Kroemer; A Marabelle; S Michiels; A Cavalcanti; M J Smyth; J S Weber; A M Eggermont; L Zitvogel Journal: Nat Commun Date: 2017-09-19 Impact factor: 14.919