Expression of c-FLIP in malignant melanoma, and its relationship with the clinicopathological features of the disease

Background. Numerous molecular events have been associated with the development of malignant melanoma (MM). The cellular FLICE-like inhibitory protein (c-FLIP) was originally identified as an inhibitor of death-receptor signalling through competition with FADD-like interleukin-1 beta-converting enzyme (FLICE; also known as caspase-8) for recruitment to the FAS-associated death domain (FADD), and it has been suggested recently that c-FLIP is required for the survival and proliferation of various cell types. Aim. To investigate the relationship of c-FLIP expression with the clinicopathological features of MM. Methods. Immunohistochemical staining with anti-c-FLIP antibody was performed on tissue samples taken from 77 MMs and 20 naevi. The proliferative cells were visualized by staining with Ki-67 antibody. Annexin V-propidium iodide labelling, a marker for chromatin condensation, was performed to observe the rate of cell apoptosis by flow cytometry. Results. Expression of c-FLIP was increased in MM tissue compared with the matched pigmented naevi. The c-FLIP expression was significantly associated with the histological type and Clark level of MM, and correlated strongly with the Ki-67 labelling index. Downregulation of c-FLIP might increase apoptosis in MM cell lines. Conclusions. c-FLIP might play an important role in the obtaining of aggressive biological behaviours and be useful in predicting prognosis of patients with MM.