Expression of thymidine phosphorylase as an indicator of poor prognosis for patients with transitional cell carcinoma of the bladder

BACKGROUND, Thymidine phosphorylase (TP), which is identical to platelet-de rived endothelial cell growth factor (PD-ECGF), stimulates chemotaxis of en dothelial cells and is involved in the angiogenesis of human solid tumors. METHODS. The activity and expression of TP were examined in human transitio nal cell carcinomas (TCCs) of the bladder, and their association with clini copathologic findings was determined. The activity of the enzyme in 37 TCCs and 12 adjacent nonneoplastic tissues was measured spectrophotometrically. The expression of TP was also examined by immunoblotting. Immunohistochemi cal analysis was performed on 108 TCCs. RESULTS. TP activity in the carcinomas was higher than that in adjacent nor mal tissues (P = 0.002). TP activity in Grade 3 tumors or those classified as pT2-4 was higher than in Grade I and 2 tumors (P = 0.017) or those class ified as pT1 (P = 0.007). The level of expression of TP detected by immunob lotting correlated well with TP activity. Immunohistochemical analyses show ed that 62 of 108 cases (57.4%) were TP positive. There was a significant c orrelation between TP expression and histologic grade, infiltration pattern , local invasion, and lymph node metastasis. TP expression as a prognostic variable was studied using the Cox proportional hazards model. TP overexpre ssion was an independent prognostic factor, as were lymph node metastasis a nd local invasion. CONCLUSIONS. These findings suggest that TP activity and its level of expre ssion influence the progression of TCC and the prognoses of patients with t his disease. (C) 2000 American Cancer Society.