CORRELATION BETWEEN THYMIDINE PHOSPHORYLASE EXPRESSION AND PROGNOSIS IN HUMAN RENAL-CELL CARCINOMA

Purpose: Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. We examined whether TP expression in renal cell carcinoma (RCC) is as sociated with microvessel density as a marker of angiogenesis, clinico pathologic characteristics, and outcome, Patients and Methods: The enz ymatic activity and expression of TP were examined in 18 RCCs and 19 k idney tissues not grossly involved with tumor from 24 patients with 13 paired samples and 11 unpaired samples by spectrophotometry and immun oblotting, The relationship between TP expression and microvessel dens ity was assessed by immunohistochemistry in 133 RCCs, Results: The med ian enzymatic activity of TP in RCCs was nine fold higher than that in nonneoplastic kidney tissues (P < .001), Similar results were obtaine d by immunoblot analysis. According to the TP staining profile, tumors were classified as no or low, intermediate, or high TP-expressing tum ors, TP positivity was significantly correlated with microvessel densi ty, TP expression was correlated with tumor grade, but there was no si gnificant association between TP expression and other clinicopathologi c characteristics. TP expression as a prognostic variable was studied using Cox's proportional hazards model, TP overexpression was on indep endent prognostic factor (hazards ratio, 3.95; 95% confidence interval , 0.98 to 15.89; P = .039) as were nodal category, metastases category , tumor grade, and venous invasion. Conclusion: These findings suggest that TP expression is correlated with microvessel density in RCC and is an unfavorable independent prognostic factor. The future developmen t and characterization of TP inhibitors may provide a novel approach t o the therapy of RCC. (C) 1997 by American Society of Clinical Oncolog y.