p53 alterations in porokeratosis.
BACKGROUND
Porokeratosis (PK) is a group of cutaneous entities characterized by disordered epidermal keratinization and by a predisposition to develop malignant transformation. The molecular mechanism of this carcinogenesis remains unclear, but p53 has been proposed as a mediator of this process. p53 overexpression, detected by immunohistochemistry, has frequently been reported in PK, and p53 mutations are direct results of ultraviolet (UV) skin exposure and are directly involved in most common skin cancers.


METHODS
Eleven cases of Mibelli-type PK, one of them associated with a squamous cell carcinoma, were reviewed. Formalin-fixed, paraffin-embedded archival tissue from these cases was immunostained for p53 and used for DNA extraction for the analysis of p53 mutations by polymerase chain reaction and single-strand conformation polymorphism.


RESULTS
Increased p53 expression was confirmed in all cases. Most of them showed a discontinuous labeling, often stronger at the base of the cornoid lamella. No relation with sun exposure was observed. Finally, no p53 mutations were found at the gene levels more frequently damaged in human cancers called "hot spots".


CONCLUSIONS
p53 alterations can be involved in the pathogenesis of the PK and the carcinogenesis arising in some of the lesions. Since p53 gene inactivation in human cancer is related to mutation and/or loss, the absence of genetic damage could indicate that p53 alterations are only at the protein level, leading to an abnormal cell-cycle control. UV exposure does not seem to play a main role in the process.
Arranz-Salas
Isabel
I
Department of Pathology, Hospital Carlos Haya, Avenida Carlos Haya s/n, 29010 Málaga, Spain.
Sanz-Trelles
Andres
A
Ojeda
Dolores Bautista
DB
D000293:Adolescent; D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017499:Porokeratosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53