CLINICOPATHOLOGICAL AND PROGNOSTIC-SIGNIFICANCE OF AN ANGIOGENIC FACTOR, THYMIDINE PHOSPHORYLASE, IN HUMAN COLORECTAL-CARCINOMA

Background: Platelet-derived endothelial cell growth factor (PD-ECGF) is known to promote the development of new blood vessels, which are fu ndamental to tumor growth and metastasis. We previously found that thy midine phosphorylase (dThdPase) acid PD-ECGF are the same protein. Pur pose: We retrospectively examined the expression of dThdPase in primar y colorectal carcinomas, its association with angiogenesis and clinico pathologic findings, and its prognostic value. Methods: Tissues were o btained from the tumors of 163 patients whose colorectal carcinomas we re completely removed by surgery. Microvessels assessed by immunostain ing endothelial cells for factor VIII were counted on a 400x field in the most active areas of neovascularization within the tumor. We purif ied the monoclonal antibody against dThdPase and studied the expressio n of dThdPase in the same serial sections used for the detection of fa ctor VIII. Those who carried out microvessel counting and dThdPase exp ression assessment had no knowledge of clinicopathologic findings. The significance of dThdPase in the prognosis of patients with colorectal carcinomas was also examined in the survival analysis of mortality fo llow-up data covering the period between 1984 through 1991. Reported P values are from two-sided tests of statistical significance. Results: The mean microvessel count (+/- standard deviation) in dThdPase-posit ive colorectal carcinoma specimens (17.5 +/- 7.2) was higher (P<.001) than that in dThdPase-negative carcinoma specimens (9.3 +/- 5.5). The dThdPase positivity was in accordance with the microvessel count. dThd Pase positivity showed highly significant statistical associations wit h tumor size, extent of invasion, lymph node metastasis, lymphatic inv asion, and venous invasion. Cox regression analysis revealed that dThd Pase expression was prognostic for poor disease outcome after adjustme nt for Dukes' stage and microvessel count. Conclusions: These findings suggest that higher levels of dThdPase expression in colorectal carci nomas are associated with more extensive angiogenesis, poor clinical a nd laboratory findings, and unfavorable clinical outcome. Implications : Inhibition of dThdPase in human colorectal carcinomas might improve prognosis for some patients.