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

Clin Exp Dermatol. 2012 Apr;37(3):259-65. doi: 10.1111/j.1365-2230.2011.04238.x. Epub 2011 Nov 21.

Abstract

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-1β-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
  • Cell Proliferation
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Neoplasm Proteins / metabolism*
  • Nevus, Pigmented / metabolism
  • Nevus, Pigmented / pathology
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Ki-67 Antigen
  • Neoplasm Proteins