Clinical significance of thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in transitional cell cancer

Purpose: Thymidine phosphorylase (TdR-Pase) and dihydropyrimidine dehydrogenase (DPD) are thought to be key enzymes in the metabolic pathways of 5-fluorouracil (5-FU). Theoretically, tumors which have low DPD and/or high TdR-Pase expression should be 5-FU-sensitive. TdR-Pase also has angiogenic expression which aids tumor progression and metastasis. However, little is known concerning the relationship between DPD expression and clinical malignant potential, especially in urological cancer. Materials and methods: Transitional cell cancer (TCC) tissues were obtained from 50 patients, and TdR-Pase and DPD expression was measured by ELISA and radioenzyme assay, respectively. The sensitivity of 23 of the 50 specimens to 5-FU was assessed in a histoculture drug response assay (HDRA), an in vitro chemosensitivity test. Results: TdR-Pase and DPD expression in TCC tissues was higher than in normal urothelial tissues. The expression of both TdR-Pase and DPD in TCC increased with histological grade and stage. Superficial bladder cancer patients who had undergone transurethral resection were divided into two groups, a recurrent and a nonrecurrent group. The expression of TdR-Pase and DPD was higher in the recurrent group than in the nonrecurrent group, but the differences were not significant. There was a significant inverse correlation between DPD expression and 5-FU sensitivity. However, TdR-Pase exhibited no correlation with 5-FU sensitivity. Conclusions: The expressions of both enzymes may be a good indicator of the malignant potential of TCC. Although DPD may be a good indicator of sensitivity of TCC to 5-FU, TdR-Pase appeared not to regulate the sensitivity of TCC to 5-FU.