In situ gene expression of urokinase-type plasminogen activator and its receptor in transitional cell carcinoma of the human bladder

The urokinase-type plasminogen activator (uPA) system plays a central role in the blood clot dissolution and tissue plasticity. uPA is a serine protease that is also involved in the metastatic process upon activation and binding to its receptor (uPAR). Studies have shown that levels of uPA in malignant tumors are higher than in the corresponding normal tissue or in benign tumors of the same tissue. We investigated uPA and uPAR gene expression in 20 human transitional cell carcinomas (TCC) of the bladder (n=19) and the renal pelvis (n=1) in comparison with adjacent nonmalignant tissues. We performed mRNA in situ hybridization (isH) and immunohistochemical staining. uPA-mRNA and uPAR-mRNA were present in 95% (19/20) and 85% (17/20) of the TCC samples, respectively and significantly higher expressed than in the adjacent normal tissue. uPA-mRNA was expressed only in malignant urothelial cells, whereas uPAR-mRNA was localized in malignant urothelial cells as well as in surrounding stromal cells. There was a statistically significant lower expression of uPA/uPAR-protein in adjacent normal tissue. Strong uPAR-protein signal intensity was related to a marked protein expression as semi-quantitatively determined by immunohistochemistry. For uPA-protein this observation was less frequent. There was a statistical trend that higher expression of uPA and uPAR corresponded with tumor stage and grade of TCC. Statistical significance was reached for uPAR-antigen compared to tumor stage (p=0.025). We conclude that higher expression of uPA and uPAR could indicate a more aggressive phenotype of TCC.