The p53 Signalling Pathway in Cutaneous Basal Cell Carcinoma: An Immunohistochemical Description

Abstract

Basal cell carcinoma (BCC) is the most common malignant tumour of the skin. The incidence of BCC is increasing, and the disease represents a major medical and economic problem. UV radiation and other genotoxic agents have been shown to cause different types of both direct and indirect DNA damage (1), including the generation of pyrimidine dimers and DNA double-strand breaks (DSBs). In addition to mutations in the sonic hedgehog pathway, which represent the molecular hallmark of BCC pathogenesis, mutations in the p53 gene are frequently detected in these malignancies. However, the relevance of this finding is not completely understood; thus, the aim of this investigation was to elucidate the relevance of the p53 pathway in the pathogenesis of BCC by immunohistochemically analysing the expression of some major proteins involved in p53-mediated cellular signalling, namely p53, ΔNp63, TAp73, and MDM2. Because p53 is activated by DNA damage to either arrest the cell cycle or induce apoptosis, we also immunohistochemically analysed the expression of γ-H2AX, an early sensor of DNA damage.