The significance of thymidine phosphorylase/platelet‐derived endothelial cell growth factor activity in renal cell carcinoma

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Abstract
BACKGROUND Thymidine phosphorylase (TP) is identical to platelet‐derived endothelial cell growth factor (PDECGF) and has angiogenic activity. Little is known about the significance of TP/PDECGF activity in patients with renal cell carcinoma (RCC). The authors examined the enzymatic activity of TP in 66 RCC specimens and investigated the association between the level of TP activity and the stage/grade status of patients with RCC. Furthermore, the authors examined the correlation between TP/PDECGF activity and prognosis. METHODS TP activity levels in nonfixed, fresh‐frozen RCC specimens and in specimens of normal kidney were determined using a thin‐layer chromatography assay. RESULTS The activity of TP was approximately 3.5‐fold greater in RCC specimens compared with normal kidney specimens. TP activity in patients with Stage III–IV RCC was 2.6‐fold greater compared with TP activity in patients with Stage I–II RCC. In addition, the level of TP activity was correlated with a higher grade of RCC. Patients who had RCC with low TP activity had a longer postoperative disease‐specific survival compared with patients who had RCC with high TP activity in the 5‐year follow‐up. CONCLUSIONS The current study is the first to demonstrate a correlation between levels of TP activity and both disease progression and a higher grade of RCC. It also is the first to show that elevated TP activity in patients with RCC predicts a poor prognosis. The results suggest that high TP/PDECGF activity may be associated with the malignant potential of RCC and that TP/PDECGF may be a molecular therapeutic target in patients with RCC. Cancer 2003;98:730–6. © 2003 American Cancer Society. DOI 10.1002/cncr.11570