THE RELATION BETWEEN P53-MUTATION AND P53-IMMUNOSTAINING IN NONMELANOMA SKIN-CANCER

Extensive study of the p53 gene has established its role as a tumour-s uppressor gene, and the involvement of mutant p53 in a wide spectrum o f human malignancy. Many mutations of p53 result in a protein product that is abnormally stable, so that it becomes readily detectable by im munocytochemistry. In contrast, under normal conditions, it has been c onsidered that levels of wild-type p53 were too low to be detectable. Although positive immunocytochemistry has been used as a marker of mut ation, recent evidence suggests that this assumption may not always be valid. We have carried out both PCR-sequencing of exons 5-8 of the p5 3 gene in 20 basal cell carcinomas (BCC), and immunocytochemistry of t hese tumours with the anti-p53 antibody DO7. Twenty cases of Bowen's d isease, in which we had previously documented mutations, were also imm unostained. We report a low rate of p53 mutation in the BCCs we examin ed (2/20), and a discrepancy between tumours with positive immunostain ing and those with mutation in both Bowen's disease and BCC. Of eight tumours in which we detected mutation, only four were immunopositive: of 19 immunopositive samples, only four showed detectable mutation. We discuss the implications of our results for the use of positive immun ostaining in clinical diagnosis, and the involvement of p53 in skin ca rcinogenesis.