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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 134 (1996), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary The proto-oncogene c-kit encodes the transmembrane tyrosine kinase receptor that has a role in the growth regulation of various cell types including melanocytes. In the present study we have examined the expression of the c-kit protein in the skin of seven patients with vitiligo. Melanocytes positive for c-kit protein were observed in the basal layer in non-lesional skin and the mean number of 25.8 ± 5·2 (per 200 basai ceils) compared with that of 21·8 ± 3·5 from six control subjects. In perilesional skin there was a reduction in the numbers of c-kit positive melanocytes (6·7±2·6) and this was especially noticeable in six of the seven patients. Such a reduction was less obvious following staining with MEL-5 and in only two subjects were the numbers of melanocytes below the normal range. This suggests that the reduction in c-kit staining was the result of decreased expression of the protein rather than a loss of melanocytes. No melanocytes. positive for c-kit protein, or after staining with MEL-5. were identified in lesional skin although isolated tyrosinase-positive melanocytes were seen in one subject. There was no apparent change in the numbers of mast ceils expressing c-kit protein and the intensity of staining in the dermis even in lesional skin was similar to that in the controls. These results demonstrate that c-kit protein is present on melanocytes in adult human skin and that in perilesional skin of some vitiligo patients there is a reduction in the numbers of melanocytes expressing this receptor. Whether this may contribute to the defective melanocyte growth and/or survival that occurs in vitiligo or whether it is a consequence of melanocyte damage remains to be seen.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 129 (1993), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Extensive study of the p53 gene has established its role as a tumour-suppressor gene, and the involvement of mutant p53 in a wide spectrum of human malignancy. Many mutations of p53 result in a protein product that is abnormally stable, so that it becomes readily detectable by immunocytochemistry. In contrast, under normal conditions, it has been considered that levels of wild-type p53 were too low to be detectable. Although positive immunocytochemistry has been used as a marker of mutation, recent evidence suggests that this assumption may not always be valid. We have carried out both PCR-sequencing of exons 5-8 of the p53 gene in 20 basal cell carcinomas (BCC), and immunocytochemistry of these tumours with the anti-p53 antibody Do7. Twenty cases of Bowen's disease, in which we had previously documented mutations, were also immunostained. We report a low rate of p53 mutation in the BCCs we examined (2/20), and a discrepancy between tumours with positive immunostaining and those with mutation in both Bowen's disease and BCC. Of eight tumours in which we detected mutation, only four were immunopositive; of 19 immunopositive samples, only four showed detectable mutation. We discuss the implications of our results for the use of positive immunostaining in clinical diagnosis, and the involvement of p53 in skin carcinogenesis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 128 (1993), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: ras mutations have been reported as an early event in some human malignancies and in the mouse skin model of multistep carcinogenesis; early studies in human non-melanoma skin cancers have reported variable rates of ras mutations. A recent study, however, has reported a high frequency of activating mutations of the Harvey-ras proto-oncogene in non-melanoma skin cancers, and the site specificity of the mutation at the second position of codon 12 prompted us to re-examine the importance of Ha-ras codon 12 mutations as an early event in the development of these tumours, using a combination of PCR and restriction fragment polymorphism of codon 12 of the Ha-ras gene. Dilution experiments confirmed that the method was sensitive and capable of detecting mutations at this codon when only 4% of the total alleles are mutated. We were surprised to find no mutations in the 40 basal cell carcinomas. 12 squamous cell carcinomas and 12 cases of Bowen's disease studied. We conclude that Ha-ras codon 12 mutations are rare events in human non-melanoma skin cancer in the U.K. The marked differences in the frequency of codon 12 Ha-ras mutations in published studies may relate to either technical artefacts, or differences in the molecular epidemiology between areas of low and high sun exposure.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 128 (1993), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The skiu affords an excellent model of human carcinogenesis because a variety of lesions from benign tumours to invasive malignancy, with or without metastatic potential, are commonly found, and are accessible to biopsy. To date, few genetic alterations have been observed in skin neoplasia. In this study we have used a recently developed monoclonal antibody (DO7) to examine p53 protein expression in a wide variety of benign and malignant skin lesions. Benign skin lesions were negative, but a significant number of malignant epithelial lesions showed detectable p53: 56% of squamous carcinomas and 42% of basal cell carcinomas were positive. A smaller proportion of dysplastic epithelial lesions were positive (27%). and only 3.6% of malignant melanomas were positive. Thus, although detectable p53 protein is a common occurrence in malignant epithelial lesions, it does not correlate with the malignant phenotype or with metastatic potential. 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.
    Type of Medium: Electronic Resource
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