EXPRESSION OF P53 IN UROTHELIAL CELL-CULTURES FROM TUMOR-BEARING AND TUMOR-FREE PATIENTS

An explant culture technique was used to culture normal urothelium fro m patients with muscle-invasive bladder cancer (transitional cell carc inoma, TCC) (n = 11) and from non-tumour-bearing patients (n = 60). Ce ll cultures were examined for expression of p53 using the monoclonal a ntibody p53-240. There was a statistically significant increase in p53 expression in normal urothelial cell cultures from patients with TCC (P < 0.0005). Normal urothelial cultures from patients with TCC also s howed more rapid proliferation in vitro when compared with non-tumour- bearing patients (P < 0.0005). A subgroup of non-tumour-bearing patien ts (n = 14) showed > 5% of cells expressing p53, p53 expression in thi s subgroup was found to correlate with cell proliferation in vitro (r( 2) = 0.766). None of these urothelial specimens was observed to expres s p53 when paraffin-embedded preparations were stained with p53-D07 an tibody prior to culture. The rate of cellular proliferation in this su bgroup did not differ from that of normal urothelium from TCC patients . Twenty-two paraffin-embedded, muscle-invasive TCC specimens were als o evaluated for p53 expression using p53-D07. The expression of p53 in these tumours did not differ from that observed in normal urothelial cell cultures from patients with TCC (P = 0.26). This study identifies an overexpression of p53 in normal urothelial cells from patients wit h TCC and in proliferating cultures from a significant subgroup of pat ients without malignant disease. Increased p53 expression in normal cu ltured urothelial cells from patients with bladder cancer implies a gl obal change in the mechanisms controlling urothelial cell division. Th is may represent an early step in the pathway to carcinogenesis.