P53 ONCOPROTEIN EXPRESSION AND GENE-MUTATIONS IN SOME KERATOACANTHOMAS

Objective: To analyze the relationship of p53 oncoprotein overexpressi on in most keratoacanthomas (KAs) with gene mutations. Design: Express ion of p53 oncoprotein in immunohistochemical staining and its correla tion to gene mutations in DNA extracted from KAs and tested in single- strand conformational polymorphism (SSCP) analysis and direct sequenci ng. Setting: A micrographic surgery unit and a dermatopathology unit a t a university medical center. Patients: Sixteen formalin-fixed, paraf fin-embedded skin biopsy specimens were retrieved from dermatopatholog y archives. Biopsies were performed to establish the diagnosis of KA b efore surgical treatment. Main Outcome Measures: Intensity of staining in immunohistochemical testing for p53 oncoprotein expression and seq uencing of gene mutations. Results: Immunohistochemical staining of 16 KA specimens detected p53 oncoprotein in 15 (94%), distributed as str ong in 4 (25%), moderate in 2 (12%), mild in 9 (56%), and negative in 1 (6%), compared with control specimens. Specimens were screened by SS CP for mutations in the p53 gene, and 1 specimen showed a potential mu tation in exon 7. Direct sequencing of the samples revealed 2 point mu tations. One specimen showed a change of G:A for A:G in codon 146 of e xon 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 tyrosine for aspar agine. Conclusions: Ninety-four percent of KA specimens evaluated had detectable p53 oncoprotein. This protein was associated with a point m utation in the p53 gene in 2 of 16 KAs evaluated. In a small fraction of KAs, overexpression of p53 oncoprotein may be associated with point mutations in the p53 gene.