Impaired ΔNp63 expression associates with reduced β-catenin and aggressive phenotypes of urothelial neoplasms

p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a ΔN-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, ΔNp63 expression predominated over TAp63, and amounts of ΔNp63 mRNA correlated with p63 immunoreactivity, confirming that ΔNp63 accounts for p63 expressed in urothelial tissues. In cultured cells, ΔNp63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired ΔNp63 expression significantly associated with reduced β-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired ΔNp63 expression characterises aggressive phenotypes of urothelial neoplasms.