Expression of cathepsin D in urothelial carcinoma of the urinary bladder: an immunohistochemical study including correlations with extracellular matrix components, CD44, p53, Rb, c-erbB-2 and the proliferation indices.

The immunohistochemical Cathepsin D (CD) expression of tumor and stromal cells was investigated in a series of 77 urothelial carcinomas of the urinary bladder with the intention to evaluate its prognostic significance and its contribution to the metastatic potential of bladder cancer. CD expression (clone D13A) was correlated with the expression of extracellular matrix components (collagen type IV, laminin, fibronectin), CD44, p53, pRb, proliferation indices (PCNA and MIB1) as well as with other conventional clininopathological features. CD expression (> 10% of positive tumor cells) was observed in 77.9% of the carcinomas. Stromal CD expression was detected in all cases. Linear collagen type IV and laminin deposit at the tumor-stroma border (in > 25% of the BM) was found in 26% and 57.6% of the cases, respectively. The CD of cancer cells (CCCD) was inversely-correlated with the CD of the stromal cells (p = 0.039), tumor grade (p = 0.0028), tumor stage (p = 0.0046), p53 protein (p = 0.05) and positively-correlated with CD44 (p = 0.002) and pRb (p = 0.05). The stromal cells CD (SCCD) showed a statistically significant positive correlation with tumor grade (p < 0.0001) and stage (p = 0.0001), and the proliferation indices PCNA and MIB1 (p = 0.0001 and p = 0.0002, respectively). These data suggest that both CD of tumor and stromal cells could play important roles in the expansion of urothelial carcinoma of the urinary bladder.