Expression of cathepsin D in transitional cell bladder tumours.

Biopsy specimens from 177 bladder tumours were analysed by immunohistochemical methods for the expression of cathepsin D. Strong expression of cathepsin D was detected in transitional carcinoma cells in 40 per cent of cases. Umbrella cells were positive in 29 per cent of cases and a cathepsin D-positive cell zone composed of tissue macrophages was detected at the invasion front in 34 per cent of tumours. Strong expression of cathepsin D was related to muscle invasive growth phase (T > or = 2) (P = 0.019), grade 2-3 histology (P = 0.008), S-phase fraction over 10 per cent (P = 0.032), and overexpression of epidermal growth factor receptor (EGFR) (P < 0.001). Umbrella cells were positive in low-grade (P = 0.03) papillary tumours (P = 0.02) with an S-phase fraction < or = 10 per cent (P = 0.02). Cathepsin D was expressed in macrophage-like cells in the invasion front in tumours which were densely infiltrated by inflammatory cells (P = 0.017) and in tumours overexpressing EGFR (P = 0.017) or p53 protein (P = 0.007). Progression in N- (P = 0.04) and M-categories (P = 0.01) was related to strong expression of cathepsin D in cancer cells and in univariate survival analysis; this was weakly related to poor outcome (P = 0.09). In multivariate analysis, papillary status (P = 0.055) and S-phase fraction (P = 0.079) predicted prognosis in Ta-1 tumours. In T2-4 tumours, T-category (P < 0.001), papillary status (P < 0.001), S-phase fraction (P = 0.028), and the presence of cathepsin D-positive tissue macrophages (P = 0.017) were independent prognostic factors.