P53 oncoprotein expression and gene mutations in some keratoacanthomas.

OBJECTIVE

To analyze the relationship of p53 oncoprotein 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 oncoprotein expression and sequencing of gene mutations.

RESULTS

Immunohistochemical 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 tyrosine for asparagine.

CONCLUSIONS

Ninety-four percent of KA specimens evaluated had detectable p53 oncoprotein. 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 oncoprotein may be associated with point mutations in the p53 gene.