p53 Oncoprotein expression and gene mutations in some keratoacanthomas

Objective: To analyze the relationship of p53 ancoprotein overexpression in most keratoacanthomas (KAs) with gene mutations. Design: Expression of p53 oncoprotein in immunohistochemical staining and its correlation to gene mutations in DNA extracted from KAs and tested in single-strand conformational polymorphism (SSCP) analysis and direct sequencing. Setting: A micrographic surgery unit and a dermatopathology unit at a university medical center. Patients: Sixteen formalin-fixed, paraffin-embedded skin biopsy specimens were retrieved from dermatopathology archives. Biopsies were performed to establish the diagnosis of KA before surgical treatment. Main Outcome Measures: Intensity of staining in immunohistochemical testing for p53 ancoprotein expression and sequencing of gene mutations. Results: lmmunohistochemical staining of 16 KA specimens detected p53 oncoprotein in 15 (94%), distributed as strong in 4 (25%), moderate in 2 (12%), mild in 9 (56%), and negative in 1 (6%), compared with control specimens. Specimens were screened by SSCP for mutations in the p53 gene, and 1 specimen showed a potential mutation in exon 7. Direct sequencing of the samples revealed 2 point mutations. One specimen showed a change of G:A for A:G in codon 146 of exon 5, predicting an amino acid substitution of tryptophan for a stop codon. Another specimen revealed a change of T:A for A:T in codon 234 of exon 7, predicting an amino acid substitution of tyro-sine for asparagine. Conclusions: Ninety-four percent of KA specimens evaluated had detectable p53 ancoprotein. This protein was associated with a point mutation in the p53 gene in 2 of 16 KAs evaluated. In a small fraction of KAs, overexpression of p53 ancoprotein may be associated with point mutations in the p53 gene.