TP53 ALLELE LOSS, MUTATIONS AND EXPRESSION IN MALIGNANT-MELANOMA

p53 alterations at the DNA, mRNA and protein levels were studied in tu mour metastases sampled from 30 patients with malignant melanoma. Para ffin-embedded sections from these and an additional 12 patients were e xamined for the presence of p53 protein. TP53 gene aberrations were fo und in 7 of 30 (23%) of the patients, six of which showed loss of hete rozygosity (LOH). Point mutations were detected in only two cases, one of which had LOH whereas the other was non-informative. Increased lev els of p53 mRNA were present in only one tumour with, but in six cases without, detectable DNA abnormalities. Four of the latter and six tum ours with normal transcript levels had immunohistochemically detectabl e levels of p53 protein. In 25 cases in which corresponding primary an d metastatic lesions could be compared, closely similar immunoreactivi ty patterns were observed. Increased expression of the MDM2 gene was f ound in only one tumour in parallel with overexpression of p53. Altoge ther, the data indicate that inactivation of the p53 regulatory pathwa y is not of major significance in the tumorigenesis of malignant melan oma. However, a significant association was found between p53 immunore activity and the relapse-free period in patients with superficial spre ading melanoma. That increased protein expression was predominantly fo und in tumours without DNA alterations might suggest a role for the wi ld-type p53 protein in restricting malignant cell proliferation in the se cases.