Abstract
p53 alterations at the DNA, mRNA and protein levels were studied in tumour metastases sampled from 30 patients with malignant melanoma. Paraffin-embedded sections from these and an additional 12 patients were examined for the presence of p53 protein. TP53 gene aberrations were found in 7 of 30 (23%) of the patients, six of which showed loss of heterozygosity (LOH). Point mutations were detected in only two cases, one of which had LOH whereas the other was non-informative. Increased levels of p53 mRNA were present in only one tumour with, but in six cases without, detectable DNA abnormalities. Four of the latter and six tumours with normal transcript levels had immunohistochemically detectable levels of p53 protein. In 25 cases in which corresponding primary and metastatic lesions could be compared, closely similar immunoreactivity patterns were observed. Increased expression of the MDM2 gene was found in only one tumour in parallel with overexpression of p53. Altogether, the data indicate that inactivation of the p53 regulatory pathway is not of major significance in the tumorigenesis of malignant melanoma. However, a significant association was found between p53 immunoreactivity and the relapse-free period in patients with superficial spreading melanoma. That increased protein expression was predominantly found in tumours without DNA alterations might suggest a role for the wild-type p53 protein in restricting malignant cell proliferation in these cases.
Highlights
Summary p53 alterations at the DNA, mRNA and protein levels were studied in tumour metastases sampled from 30 patients with malignant melanoma
DNA from 30 matched pairs of melanoma metastases and peripheral blood cells was studied for loss of heterozygosity (LOH) on chromosome fragment 17p
It has been suggested that the TP53 gene located on chromosome 17 may be involved in melanoma development, as a high fraction of tumour samples studied by immunohistochemistry stained positively for p53 protein, indicating p53 aberrations (Stretch et al, 1991; Akslen &M0rkve, 1992)
Summary
Summary p53 alterations at the DNA, mRNA and protein levels were studied in tumour metastases sampled from 30 patients with malignant melanoma. Increased levels of p53 mRNA were present in only one tumour with, but in six cases without, detectable DNA abnormalities. Four of the latter and six tumours with normal transcript levels had immunohistochemically detectable levels of p53 protein. That increased protein expression was predominantly found in tumours without DNA alterations might suggest a role for the wild-type p53 protein in restricting malignant cell proliferation in these cases. The aim of the present work was to study a panel of malignant melanomas of different histological subtypes and at different stages of disease progression for TP53 allele deletions, gene mutation and the tumour levels of p53 mRNA and protein. Attempts were made to relate the p53 status to the mRNA expression of mdm and to known clinical parameters for melanoma progression
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