EXPRESSION OF THE ANGIOGENIC FACTOR THYMIDINE PHOSPHORYLASE PLATELET-DERIVED ENDOTHELIAL-CELL GROWTH-FACTOR IN PRIMARY BLADDER CANCERS/

Thymidine phosphorylase (TP), also known as platelet-derived endotheli al cell growth factor, has been implicated in bladder cancer angiogene sis. To examine its role more clearly, we have quantified and localize d its expression using Western analysis and immunohistochemistry in a series of 105 bladder cancers. We have also assessed the relationship between TP expression and other tumor parameters including quantitativ e angiogenesis, p53 status, ploidy, and survival. By Western analysis, TP expression was 5-fold higher in tumors than in normal bladder samp les (P < 0.02). Expression was 15-fold higher in invasive tumors than in normal bladder (P < 0.001) and 8-fold higher than in superficial tu mors (P < 0.005). Immunohistochemistry of the tumors showed TP was pre sent in the neoplastic epithelium in 27% of the tumors, in the inflamm atory cells in 72% of the tumors, in stromal cells in 30% of the tumor s, and in tumor-associated endothelium in 11% of the tumors. Expressio n by Western blotting and immunohistochemistry was significantly up-re gulated in tumors compared with normal bladder (P < 0.05). Tumor cell TP expression correlated with tumor grade (P < 0.02), but there was no correlation between tumor cell TP expression and tumor stage (P = 0.4 6), ploidy (P = 0.52), p53 expression (P = 0.9), tumor vascularity (P = 0.8), relapse-free survival (P = 0.57), or overall survival (P = 0.9 4). TP protein is expressed in bladder cancers, and expression is asso ciated with an aggressive phenotype. Because TP can activate a number of cytotoxic agents, it provides a potential therapeutic target in bla dder cancer.