P53 GENE MUTATION AND EXPRESSION IN NEVI AND MELANOMAS

Mutations of the p53 tumour suppressor gene are common to many human m alignancies. Although increased p53 expression has been observed in cu taneous malignant melanoma, mutations of the p53 gene appear to be inf requent, We ex-amined 140 benign and malignant paraffin-embedded melan ocytic lesions for p53 protein expression by immunohistochemistry, usi ng the monoclonal anti-p53 antibody DO-7 and a microwave method of ant igen retrieval, Fifteen naevi and 25 melanomas were further analysed f or p53 mutations within exons 5-8 of the p53 gene. DNA was extracted f rom paraffin sections and screening for mutations was carried out usin g 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 metas tatic lesions (15 out of 21), p53 expression in benign lesions was wea ker than in malignant lesions in intensity and percentage of cells sta ining, p53 protein expression in melanomas increased in intensity and percentage of cells staining with tumour progression. In 25% (three ou t of 12) of metastatic melanomas p53 mutations were detected by PCR-SS CP and increased expression of p53 protein was observed in these tumou rs, p53 gene mutations were not detected in any benign melanocytic les ions, We demonstrate that antigen retrieval techniques increase p53 im munoreactivity in paraffin embedded melanocytic tissues, p53 protein e xpression in melanomas increases with depth of tumour invasion. As p53 gene mutations occur infrequently in malignant melanoma, other mechan isms are proposed to influence p53 protein expression in melanocytic l esions.