The activity of thymidine phosphorylase (TdR-Pase), which is identical to platelet-derived endothelial cell growth factor (a potent angiogenic factor), was analyzed in primary human bladder cancer tissues. TdR-Pase activity in tissues was determined from the conversion rate of 5'-deoxy-5-fluorouridine to 5-fluorouracil. The mean activity in 37 bladder cancers and in 8 samples of normal bladder epithelial tissue was 108.5 and 19.2 microgram 5-fluorouracil/mg protein/h, respectively, showing a statistically significant difference. Among the cancer tissues, differences in activity were seen according to the stage and grade of tumors. Low-grade (grade 1) tumors had significantly lower activities than high-grade tumors, and high-grade invasive tumors showed significantly higher activities than low-grade superficial tumors. These results demonstrate that a high TdR-Pase activity in bladder cancer is associated with the tumor characteristics of invasion and malignant potential. Our conclusions support the hypothesis that angiogenesis that is mediated by this molecule may be involved in the development of invasive human bladder cancer, as suggested by T. O'Brien et al. (Cancer Res., 55: 510-513, 1995), and also suggest that TdR-Pase is a potential therapeutic target in human bladder cancer.

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