Abnormalities of p53 protein expression in cutaneous disorders.
Abnormalities in the p53 gene and in expression of its protein product are among the most frequent changes demonstrated in a variety of human cancers. p53 Is a nuclear phosphoprotein that in the natural form or "wild-type" can bind to DNA and prevent cells from entering into the S phase of the cell cycle. There is an increase in wild-type p53 after exposure of the skin to UV light, which allows for DNA repair before replication that would make DNA damage permanent. A loss of this protective influence destabilizes the genome. Mutation of the p53 gene commonly causes a defective protein that is degraded more slowly and accumulates in the cell to the extent that it becomes detectable by routine immunocytochemistry. These abnormalities precede the development of cancer in some examples. Studies of precursor lesions have used mainly immunohistochemical techniques that show p53 protein overexpression. The relationship between such overexpression and actual mutation of the p53 gene is controversial because overexpression of "wild-type" p53 protein also can occur. Mutations in the p53 gene have been observed in many actinic keratoses, basal cell carcinomas, and squamous cell carcinomas, and in a small proportion of malignant melanomas. Specific types of pyrimidine transitions have pointed to a role for UV light in these mutations. Molecular analysis is needed to determine whether or not immunocytochemical staining is truly reflective of mutation or is due to some other mechanism that causes an increased expression of wild-type p53.
McNutt
N S
NS
Department of Pathology, New York Hospital-Cornell University Medical Center, NY.
Saenz-Santamaría
C
C
Volkenandt
M
M
Shea
C R
CR
Albino
A P
AP
D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007636:Keratoacanthoma / Q000235:genetics; D017499:Porokeratosis / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics; D014157:Transcription Factors
D014157:Transcription Factors