Radiation-induced cutaneous carcinoma of the head and neck: is there an early role for p53 mutations?

Background. Little is known about the molecular mechanisms underlying ionizing radiation-induced carcinogenesis of the skin. Aims. To investigate the possible role of p53 in radiodermatitis and in the development of radiation-induced cutaneous carcinomas. Methods. The study group comprised six patients affected by cutaneous carcinomas arising in radiodermatitis (one squamous cell carcinoma and five basal cell carcinomas), and seven patients presenting only chronic radiodermatitis. Skin specimens were evaluated for p53 immunohistochemical expression. Using laser-assisted microdissection, areas with different p53 immunoreactivity were separately submitted to DNA isolation and p53 gene analysis. Results. In the majority of cases (9/12, 75%), p53 immunoreactivity was detected in radiation-damaged epidermis. In carcinomas p53 oncoprotein was expressed by several neoplastic cells in one case (16.7%%), or by nearly all neoplastic cells in four (66.7%). SSCP band shifts were detected in 9/25 samples (36%) microdissected from irradiated epidermis and in 3/6 (50%) carcinomas. DNA sequencing demonstrated two repeatedly found mutations: a G deletion at codon 244 and an A -> G transition at codon 205, as well as hallmarks of ultraviolet mutagenic action, including a C -> T transition occurring at a dipyrimidine site and a CC -> TT tandem double-base transition. Conclusion. Our data indicate that irradiation induces significant p53 alterations that may be relevant in the modification of epithelial maturation processes and may be responsible for the high risk for development of carcinomas in radiodermatitis.