Expression of Thymidine Phosphorylase in Human Gastric Carcinoma

Abstract

The activity of thymidine phosphorylase (dThdPase) has heen reported to increase in several types of malignant tumors. Experimental evidence has shown that dThdPase is identical to platelet‐derived endothelial cell growth factor, and that dThdPase has angiogenic activity. We examined the expression of dThdPase to investigate whether the expression of dThdPase correlates with angiogenesis, clinicopathologic features and the prognosis of patients with human gastric carcinomas. Microvessels were assessed by immnnostaining endothelial cells for factor VIII. We counted microvessels in the tumors of 158 patients whose tumors were completely removed surgically. Microvessels were counted in a × 400 field in the most active areas of neovascularization. We purified a monoclonal antibody (TMA‐1) against dThdPase and studied the expression of dThdPase using TMA‐1 in the same serial sections as those used for the detection of factor VIII. The correlation between angiogenesis and dThdPase, and the clinicopathological significance of dThdPase, in patients with gastric carcinoma were examined. The positive expression of dThdPase was more frequent (P<0.001) in gastric carcinomas (67/158, 43.4%) than that in normal tissues (12/158, 7.6%). The average microvessel count in dThdPase‐positive gastric carcinomas was higher (P<0.001) than that in dThdPase‐negative carcinomas. The percentage of gastric carcinoma cells expressing dThdPase was significantly correlated with the microvessel count (P<0.001). Further, the average size of dThdPase‐positive carcinomas was significantly larger (P<0.001) than that of negative carcinomas and the mean microvessel count in dThdPase‐positive gastric carcinomas was also significantly higher (P<0.001) than that in dThdPase‐negative carcinomas. There was a significant correlation between the positive expression of dThdPase and microvessel count (P<0.001) or lymph node metastasis (P=0.013) by multivariate logistic analysis. Further, patients with dThdPase‐positive carcinoma showed a significantly worse prognosis than those with dThdPase‐negative carcinoma overall and in stage III. These findings indicate that the expression of dThdPase in gastric carcinomas is related to progression and metastasis, and this enzyme affects the prognosis of some patients with the disease.