P53 GENE MUTATION AND EXPRESSION IN NEVI AND MELANOMAS

Mutations of the p53 tumour suppressor gene are common to many human malignancies. Although increased p53 expression has been observed in cutaneous malignant melanoma, mutations of the p53 gene appear to be infrequent, We ex-amined 140 benign and malignant paraffin-embedded melanocytic lesions for p53 protein expression by immunohistochemistry, using the monoclonal anti-p53 antibody DO-7 and a microwave method of antigen retrieval, Fifteen naevi and 25 melanomas were further analysed for p53 mutations within exons 5-8 of the p53 gene. DNA was extracted from paraffin sections and screening for mutations was carried out using PCR-SSCP, We demonstrated p53 protein expression in 33% of naevi (17 out of 51), 35% of primary melanomas (20 out of 58), and 70% of metastatic lesions (15 out of 21), p53 expression in benign lesions was weaker than in malignant lesions in intensity and percentage of cells staining, p53 protein expression in melanomas increased in intensity and percentage of cells staining with tumour progression. In 25% (three out of 12) of metastatic melanomas p53 mutations were detected by PCR-SSCP and increased expression of p53 protein was observed in these tumours, p53 gene mutations were not detected in any benign melanocytic lesions, We demonstrate that antigen retrieval techniques increase p53 immunoreactivity in paraffin embedded melanocytic tissues, p53 protein expression in melanomas increases with depth of tumour invasion. As p53 gene mutations occur infrequently in malignant melanoma, other mechanisms are proposed to influence p53 protein expression in melanocytic lesions.