EXPRESSION OF THYMIDINE PHOSPHORYLASE IN HUMAN GASTRIC-CARCINOMA

The activity of thymidine phosphorylase (dThdPase) has been reported t o 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 exam ined the expression of dThdPase to investigate whether the expression of dThdPase correlates with angiogenesis, clinicopathologic features a nd the prognosis of patients with human gastric carcinomas. Microvesse ls were assessed by immunostaining endothelial cells for factor VIII. We counted microvessels in the tumors of 158 patients whose tumors wer e completely removed surgically. Microvessels were counted in a X 400 field in the most active areas of neovascularization. We purified a mo noclonal 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 pa tients with gastric carcinoma were examined. The positive expression o f 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 micro vessel count in dThdPase-positive gastric carcinomas was higher (P < 0 .001) than that in dThdPase negative carcinomas. The percentage of gas tric carcinoma cells expressing dThdPase was significantly correlated with the microvessel count (P < 0.001). Further, the average size of d ThdPase-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 co rrelation 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-negat ive carcinoma overall and in stage III. These findings indicate that t he expression of dThdPase in gastric carcinomas is related to progress ion and metastasis, and this enzyme affects the prognosis of some pati ents with the disease.