Thymidine phosphorylase activity in renal cell carcinoma: relationship between histological parameters and chemosensitivity to fluorouracil-related drugs

Abstract.

Thymidine phosphorylase (TdR-Pase) is an essential enzyme in the metabolism of fluorouracil-related drugs and is also a potent angiogenic factor. We measured the TdR-Pase activity in human renal cell carcinomas (RCCs) to assess the relationship between TdR-Pase activity and the degree of tumor malignancy. We also investigated the relationship between TdR-Pase activity and chemosensitivity to fluorouracil-related drugs. A total of 61 RCC tissue specimens and 39 normal kidney tissue specimens were obtained. TdR-Pase activity was measured by enzyme-linked immunosorbent assay. The in vitro histoculture drug response assay was also performed to examine tumor sensitivity to 5-fluorouracil (5-FU) and doxifluridine (5′-DFUR). The TdR-Pase activity of RCCs was 13-fold that of the normal tissues. Activity increased with histological grade, and was significantly higher in high-stage tumors (T3 or higher). TdR-Pase activity exhibited a significant positive correlation with sensitivity to 5-FU and 5′-DFUR. High TdR-Pase activity in human RCC was confirmed to predict high tumor grade and stage. RCCs with high TdR-Pase activity were also sensitive to FU-related drugs.