Phosphorylation state of tumor-suppressor gene p53 product overexpressed in skin tumors

Post-transcriptional modification of p53 by phoshorylation has been proposed as an important mechanism of p53 stabilization and functional regulation. However, little is known about the phosphorylation state of mutant p53 protein overexpressed in human tumors. We evaluated immunohistochemically the p53 phosphorylation state of Ser392 and Ser15 sites in 44 actinic keratoses (AKs), 62 squamous cell carcinomas (SCCs), 23 Bowen's disease (BDs) and 43 basal cell carcinomas (BCCs). The mean labeling index (LI) of phospho-Ser392-p53 was significantly higher than that of phospho-Ser15-p53 in all cases. Phospho-Ser392-p53 protein was frequently overexpressed in not only SCCs but also AKs and BDs, revealing no significant difference in the immunoreactivity among them. In BCCs, phospho-Ser392-p53 immunoreactivity was significantly lower than that in BDs, and phospho-Ser15-p53 immunoreactivity was significantly lower than that in SCCs. Ser15 phosphorylation was significantly correlated with a high level of Ki-67 LI in BCCs. These results suggest that p53 overexpressed in skin tumors is more frequently phosphorylated at Ser392 residue than Ser15, and that the Ser392 phosphorylation is more likely to occur early in the pathogenesis of SCC. Moreover, the decreased level of the phosphorylation might be characteristic of BCC, but the Ser15 phosphorylation seems to have an influence on BCC development.