Infiltration of thymidine phosphorylase-positive macrophages is closely associated with tumor angiogenesis and survival in intestinal type gastric cancer

Abstract

Thymidine phosphorylase (TP), an enzyme catalyzing the reversible phospholysis of thymidine, deoxyuridine and their analogs at their respective bases and 2-deoxyribose-1-phosphate, thus promoting angiogenesis, is often expressed in macrophages present in tumor stroma. In this study, we investigated whether infiltration of TP-positive macrophages as well as tumor-associated macrophages affected tumor angiogenesis. TP was expressed in human macrophage-like cells, but not in gastric cancer cells in culture. The expression level of TP, the number of infiltrating CD68+ and CD163+ macrophages, and microvessel density (MVD) in the tumor were further analyzed by immunohistochemistry in 111 patients with gastric cancer. Biostatistical analysis of digitized data obtained by image analysis showed that TP expression was significantly correlated with the number of infiltrating macrophages and MVD in intestinal type gastric cancer (p<0.05). The number of infiltrating macrophages was also correlated with MVD in both the intestinal and diffuse types (p<0.05). An increased number of CD68+ macrophages was significantly associated with poor outcome in patients with intestinal type (p<0.001), but not diffuse type cancer. TP could be a specific marker enzyme that is expressed in tumor-infiltrating macrophages, being associated with tumor angiogenesis and poor prognosis in patients with intestinal-type gastric cancer.