Mutations of Fas (APO-1/CD95) and p53 genes in nonmelanoma skin cancer

Background: There is considerable evidence that apoptosis plays an important role in the pathogenesis of a wide variety of skin diseases. Apoptosis failure may ensure the survival of transformed cells prone to sustain further genetic damage and it plays an important part in the development of tumors. Genetic alterations of Fas and p53, with consequent inactivation of gene protein products, may be involved in transcriptional downregulation of Fas. Objective: We investigated Fas and its ligand expression in 30 cases of nonmelanoma skin cancer, 19 basal cell and 11 squamous cell carcinomas, and we also analyzed Fas and p53 status, in an attempt to detect putative alterations. Method: Fas and its ligand expression were evaluated by RT-PCR; the promoter and the entire coding region of Fas, and the coding exons 4-9 of p53 were investigated by polymerase chain reaction, single strand conformation polymorphism, and DNA sequencing. Results: Fas alterations were found in 3/19 (15.8%) basal cell and in 4/11 (36.4%) squamous cell carcinomas. Five out of 2 5 cases (3/19 basal cell and 2/11 squamous cell carcinomas) were p53-mutated, and in the majority of these cases there were concomitant mutations of the Fas gene (chi(2) test; p = 0.035). Conclusion: Taken together, our findings highlight an involvement of the Fas/Fas-ligand system in the development of skin cancer, suggesting that the loss of its apoptotic function, in some cases linked to p53 alterations, may contribute to the self-maintenance of cancer cells.