Heparanase protein and gene expression in bladder cancer

Purpose: We determined the association of heparanase protein and messenger (m)RNA expression with bladder cancer invasion and metastasis. Materials and Methods: The expression of heparanase protein and mRNA was as sessed by immunohistochemical staining and in situ hybridization, respectiv ely, in 67 bladder cancer specimens resected at various stages of disease. To our knowledge this is the first systematic study of heparanase protein a nd mRNA expression in human bladder cancer. Results: The expression of heparanase protein in muscular invasive bladder cancer was significantly higher than in superficial cancer (68% versus 19%, p = 0.0001). It was higher in the primary tumor of patients with lymph nod e metastatic cancer than those with nonmetastatic cancer (80% versus 37%, p = 0.0006). In high grade disease it was significantly higher than in low g rade disease (79% versus 29%, p = 0.0001). The expression of heparanase mRN A was also significantly higher in stage pT3 or greater than in stage pT2 o r less bladder cancer (96% versus 33%, p = 0.0003). In metastatic N+ cases it was significantly higher than in nonmetastatic bladder cancer (93% versu s 46%, p = 0.0037). The heparanase gene and protein showed similar patterns of expression in bladder cancer. Conclusions: Our study implies that the expression of heparanase protein an d mRNA is associated with bladder cancer invasion and metastasis, and hepar anase may have a role in disease progression.