A Study On The Expression Of Heparanase, B-FGF And UPA And Their Relationship In Bladder Transitional Cell Carcinoma

A Study on the expression of Heparanase, b-FGF and uPA and theirrelationships in bladder transitional cell carcinomaBackground: Bladder cancer is diagnosed in approximatedly 54,500 patients and results in about 11,700 deaths yearly in the United States. Although cytotoxic chemotherapy and new therapeutic tools have improved, the prognosis of patients with metastatic bladder cancer remains poor. Therefore, understanding the factors that induce metastasis is essential for developing new therapeutic methods for metastatic bladder cancer. Extracellular matrix (ECM) degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief component of the ECM. Previous studies have demonstrated heparanase expression in various malignancies and that there is differential heparanase expression between benign and malignant tumors.The first part of this study has been performed to investigate the expressions and relationship of heparanase, b-FGF and uPA in bladder transitional carcinoma(BTCC), using in situ hybridization and immunohistochemistry methods. The second part was to further determine the importance of heparanase and uPA genes in the metastasis of bladder cancer using RT-PCR method.Part I Heparanase mRNA , b-FGF and uPA Expression and significance in human bladder transitional cell carcinomaObjective: To determine the association of heparanase mRNA, b-FGF and uPA expression with human bladder cancer invasion and metastasis.Materials and Methods: Samples of 41 human bladder carcinoma and 8 normal bladder tissues were examed with in situ hybridization method for heparanse mRNA, and immunohistochemical method for b-FGF and uPA.Results: Heparanase mRNA, b-FGF and uPA positive expression rates was found 58.5%,71% and 61% in 41 BTCC specimens respectively. There were no heparanase mRNAexpressions, 2 positive b-FGF expressions and 1 positive uPA expression in 8 normal bladder tissues. The positive rates were significantly high in BTCC specimens than in normal tissues(p < 0.05). The expression of heparanase mRNA in muscular invasive bladder cancer was significantly higher than in superficial cancer (73% versus 42%, p = 0.047). It was higher in the primary tumor of patients with lymph node metastatic cancer than those with nonmetastatic cancer (89% versus 50%, p = 0.039). In high grade disease it was significantly higher than in low grade disease (69% versus 33%, p = 0.024). And significant correlations were found among heparanase, b-FGF and uPA.Conclusions: The over-expression of Heparanase mRNA, b-FGF and uPA are frequent in bladder transitional cell carcinoma. There is a significant correlation between the over-expression of Heparanase mRNA and bladder cancer's occurrence, invasion and metastasis. Heparanase, b-FGF and uPA cooperated in promoting the progression and metastasis of bladder transitional cell carcinoma.