Expression of Thymidine Phosphorylase in Human Gastric Carcinoma

Kim, Kee Hwan; Park, Cho Hyun; Kim, Jeong Soo; Lim, Keun Woo

Abstract

PURPOSE
Angiogenesis plays an important role in the growth and metastasis of solid tumors. It has been recently reported that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor. In this study, we analyzed the correlation between dThdPase activity and neovascularization, and also determined their prognostic significance by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining in patients with gastric carcinoma. METHODS: The medical records of 57 patients with gastric carcinoma who underwent radical gastrectomy were retrospectively reviewed. Primary tumors were studied by immunohistochemical staining with anti-PD-ECGF/dThdPase and anti- CD34 monoclonal antibodies. The dThdPase activity level was also analyzed by ELISA. Microvessels were assessed by immunostaining endothelial cells for CD34. We counted the number of microvessels in the tumors of the patients. RESULTS: The dThdPase activity of tumor tissues (82.4+/-66.2 unit/mg protein) was significantly higher than that of normal mucosas (8.9 +/- 18.2 unit/mg protein) (P < 0.0001). Immunohistochemical staining with anti-dThdPase and anti-CD34 monoclonal antibodies was performed in 57 gastric carcinoma tissue samples. Positive dThdPase expression was observed in 24 (42.1%) tumors. The average number of cells expressing CD34 was significantly higher in the dThdPase- positive carcinomas (44.4+/-15.3) than in the dThdPase- negative carcinomas (30.7+/-15.8)(P<0.003). The expression of dThdPase was significantly associated with the intratu moral microvessel counts (P=00005). The patients with dThdPase-positive carcinoma showed a significantly worse prognosis than those with dThdPase-negative carcinoma (P=0.034). CONCLUSION: These results suggest that dThdPase plays a role in the promotion of angiogenesis, and that it is a possible candidate as a prognostic factor in human gastric carcinomas.