We have analyzed skin lesions from RTRs with aggressive tumors for p53 gene modifications, the presence of Human Papillomas Virus (HPV) DNA in relation to the p53 codon 72 genotype and polymorphisms of the XPD repair gene.
A total of 366 unrelated individuals (177 individuals with arsenic induced keratosis and 189 individuals with no arsenic induced skin lesions) were recruited from North 24 Parganas, Nadia and Murshidabad districts between January 2003 and February 2005 for the study of the genotypic distribution of three p53 polymorphisms (16bp duplication at intron 3, codon 72 Arg/Pro and G>A at intron 6 [nt 13,494]) by PCR-RFLP.
Accumulation of p53 protein, together with an extensive apoptosis, suggests that the activation of a p53-induced apoptotic pathway may play a role in the pathogenesis of skin lesions in DLE.
This article reviews p53 alterations (at the gene and protein levels) in melanocytic skin lesions and discusses the following points: (i) p53 alterations commence as early as at the stage of benign and dysplastic nevi; (ii) these alterations are frequent in melanomas, and gradually increase with their progression; (iii) there is no concordance between the frequent p53 protein expression and the rarity of both TP53 gene mutations in melanomas, and (iv) the entire p53 pathway is a more critical determinant of the fate of the melanocytic skin lesions than the status of the p53 protein or the gene itself.
Here the authors describe an immunohistochemical study to evaluate the expression of p53 in benign and malignant skin lesions from renal transplant recipients and immunocompetent patients with skin cancer.
There was a difference in the distribution of p53 genotypes between high risk HPV-skin lesions and the controls, and the allele frequency of p53 Arg/Arg was much higher than the controls (65.5% versus 20%).
This study demonstrates that accumulation of p53 protein is frequently encountered in both premalignant and malignant skin lesions of RTRs, and that this may occur as an early step in transplant-associated skin carcinogenesis.
Because p53 tumor suppressor protein is a protective cellular molecule against environmental carcinogens and mutations in the p53 gene are frequent in nonmelanoma skin cancers, we studied p53 in 23 premalignant or malignant skin lesions from seven patients with a history of arsenic medication.
Mutations of exons 3 through 9 of the p53 gene in skin lesions were screened in 23 cases of squamous cell carcinoma (SCC), 25 cases of basal cell carcinoma (BCC), two cases of Bowen's disease, 10 cases of solar keratosis, and five cases of keratoacanthoma by polymerase chain reaction--single strand conformation polymorphism analysis.
The finding of a lower proportion of positivity in dysplastic lesions, and absence of staining in benign tumours, suggests that p53 mutation may be involved in the progression towards invasive malignancy in human squamous skin lesions.