Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atypical fibroxanthoma (AFX) is an uncommon neoplasm of the superficial soft tissue occurring in actinically damaged skin of elderly patients. Sun-exposed skin also represents the main site of squamous and basal cell carcinomas and malignant melanoma, and a key role for ultraviolet (UV) radiation in their pathogenesis has long been suspected. UV-related mutations of the p53 gene have been identified in human skin cancers. To verify whether the pathogenesis of AFX is related to the effect of sunlight, p53 protein and gene status have been investigated in a series of 10 cases of AFX. Seven of 10 showed p53 immunoreactivity in most of the neoplastic cells. Molecular analysis of the p53 gene revealed an abnormal single strand conformation polymorphism pattern in all the p53 positive cases. Polymerase chain reaction direct sequencing revealed that all the mutations involved cytosine bases. Four cases showed C to T transitions (including two CC-TT double base substitutions) and two cases showed C to G transversion. All but one mutation took place at dipyrimidine sites. These findings provide the first objective evidence for the central role of UV radiation in the development of AFX and also represent the first in vivo demonstration of solar UV-induced mutations in a human mesenchymal neoplasm.
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PMID:Ultraviolet-induced p53 mutations in atypical fibroxanthoma. 803 Jul 43

p53 mutation is one of the major results of ultraviolet (UV) radiation. UV photoproducts of cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (64PPs) also play an important role in skin cancer development. Atypical fibroxanthoma (AFX), which mimics malignant fibrous histiocytoma (MFH) histologically, occurs in the sun-exposed skin of the elderly, and therefore, an association with UV has long been suspected. Eighteen fibrohistiocytic skin lesions comprising AFX (n = 7), storiform-pleomorphic type MFH centered in the subcutis (superficial MFH; S-MFH; n = 4) and benign fibrous histiocytoma (BFH; n = 7) were used for immunohistochemical and molecular analysis. Eight cases of deep MFH (D-MFH) were also analyzed for UV photoproduct expression for the purposes of comparison. Immunohistochemically, the CPD scores of AFX (3.6 +/- 0.4) were significantly higher than those of S-MFH (1.3 +/- 0.8), D-MFH (0.8 +/- 0.5), or BHF (1.4 +/- 0.7); however, the 64PP scores were extremely low in all these tumors (AFX, 0.1 +/- 0.1; S-MFH, 0.0 +/- 0.0; D-MFH, 0.0 +/- 0.0; and BHF, 0.0 +/- 0.0). AFX, S-MFH, and BFH showed immunoexpression for p53 (2/7, 2/4, and 0/7), respectively. p53 mutations were detected in AFX (4/6; 67%) and S-MFH (1/4; 25%), but not in BFH (0/5; 0%) using polymerase chain reaction-single-strand conformation polymorphism, and all of the mutations in AFX were either C-T transitions or at dipyrimidine sites. In conclusion, AFX and S-MFH are both similar fibrohistocytic lesions; however, AFX has high immunoreactivity for CPDs compared with S-MFH, D-MFH, or BFH. These data suggest that CPDs may play an important role in the pathogenesis of AFX.
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PMID:Immunoexpression of ultraviolet photoproducts and p53 mutation analysis in atypical fibroxanthoma and superficial malignant fibrous histiocytoma. 1140 60