Flow cytometric analysis of p53 oncoprotein expression in cutaneous melanoma

Abstract

Mutation of the p53 tumour suppressor gene is thought to represent a significant step in the development of over half of all human cancers. Qualitative investigations of p53 protein in cutaneous melanoma suggest that overexpression is more common than in other tumours. This study analysed p53 protein expression using flow cytometry as a quantitative assay. Expression of p53 protein was assayed in ten benign melanocytic naevi (BMN) and 50 surgically excised ethanol-fixed melanomas. Nuclei were stained for the p53 protein with Pab1801 and analysed using flow cytometry. Protein expression was further correlated with clinicopathological parameters. None of the BMN was immunopositive for p53. Forty-one of the 50 melanomas stained positively. The overall median positivity for p53 in primary melanoma was 12.8 per cent compared with 22.5 per cent in metastatic disease. No association was found between p53 expression and Breslow thickness or presence of nodal and skin metastases. Overexpression of p53 was associated with ulceration, mitotic figures and lymphocytic infiltration, and there was a striking increase of p53 expression with age. Expression of p53 was inversely correlated with disease-free interval. Although overexpression of p53 is common in melanoma, there was no association with major clinical parameters such as Breslow thickness and overall survival. The association found between p53 and other clinicopathological features suggests that the tumour suppressor gene does play a role in the evolution of melanoma.