Fas and Fas ligand: expression and soluble circulating levels in cutaneous malignant melanoma

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Abstract
Summary 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.