Expression of p53 protein in benign and malignant epidermal pathologic conditions.

Abstract

p53 is an oncogene and a tumor-suppressor gene whose gene product regulates the cell growth cycle. Mutations in p53 are the most common genetic alterations in human cancer. Our purpose was to define p53 expression and subcellular localization in normal and pathologic epidermis. We examined sections of normal skin, psoriasis, squamous cell carcinoma (SCC), basal cell carcinoma (BCC), keratoacanthoma, and cultured epithelial cell lines with five antibodies to p53. Monoclonal antibody MAb421 and MAb1801 stained the cytoplasm of normal basal keratinocytes, suggesting that subcellular localization or sequestration of wild-type p53 regulates its activity. Polyclonal antibody reacted throughout normal epidermis, suggesting heterogeneity of species or conformational forms of p53 protein. Cytoplasmic reactivity to MAb421 was similar in normal epidermis, psoriasis, and cultured keratinocytes but was, diminished in SCC, BCC, and keratoacanthoma. CM-1 reactivity persisted in these tumors. Putative p53 mutations detected by MAb240 reactivity were present in 44% of SCC specimens. Epidermis expresses p53 and the gene may regulate epidermal keratinocyte growth and carcinogenesis.