Thymidine Phosphorylase Expression in Gallbladder Adenocarcinomas

Abstract

The expression of thymidine phosphorylase (TP), a potent chemotactic factor for endothelial cells, was studied in 60 adenocarcinomas of the gallbladder, by use of immunohistochemical techniques. Results on patterns of TP expression were correlated with angiogenesis (anti-CD31), histopathological variables, and patient survival. TP was frequently expressed in tumor cells, stromal cells, tumor-associated macrophages, and lymphocytes of gallbladder adenocarcinomas. The expression was mixed nuclear/cytoplasmic. However, only nuclear TP (TPnuc) expression by tumor cells was correlated with increased angiogenic activity. High angiogenesis, assessed as microvessel density (MVD), was the most significant prognostic factor. The subgroup of patients with TPnuc and medium/high MVD had the worst prognosis as evaluated by the survival curves. Furthermore, CD31+ lymphocytes, frequently seen in carcinomas with high-fibroblastic TP reactivity, were connected with an improved survival. It is concluded that angiogenesis, as verified by multivariate analysis, is the most important prognostic factor in gallbladder carcinomas. In these tumors, high histologic grade and low CD31+ lymphocytic infiltration are also independent predictors of poor prognosis. TP is associated with an aggressive phenotype apparently because of its anglogenic activity. Therapeutic strategies targeting TP may be of value in patients overexpressing this enzyme.

Inhibition of Metastasis of Tumor Cells Overexpressing Thymidine Phosphorylase by 2-Deoxy-l-Ribose

“…Many types of solid tumors express TP and high TP activity is correlated with microvessel density (12)(13)(14)(15). In addition to angiogenic activity, TP can suppress hypoxia-induced apoptosis (16).…”

Role of tumor angiogenesis in gallbladder carcinoma: with special reference to thymidine phosphorylase

“…[4][5][6][7] Plasma TP activity has been shown to be elevated in patients with malignant tumors. TP expression is higher in various malignant tumors than in adjacent normal tissues, and the expression is correlated with tumor growth, invasion, and metastasis.…”

“…Yamamoto et al 4 reported that TP expression was signifi cantly correlated with depth of invasion, lymph node metastasis, and tumor stage in gallbladder carcinoma, but it was not correlated with angiogenesis. Giatromanolaki et al 5 reported that gallbladder carcinoma patients with nuclear TP positivity and high MVD had the worst prognosis.…”

“…However, the mechanism of how TP and VEGF regulate angiogenesis remains unclear, and few detailed reports regarding the role of TP in gallbladder carcinoma have been published. 4,5 The aim of this study was to clarify the clinicopathological role of TP expression and to investigate the correlation between overall survival and TP expression in patients with gallbladder carcinoma. We also examined VEGF expression in gallbladder carcinoma and the relationship between TP gene expression and tissue VEGF expression.…”

“…[4][5][6][7] TP is overexpressed in various malignant tumors and its expression is correlated with tumor growth, invasion, and metastasis. Higher levels of TP expression are associated with more extensive angiogenesis, deeper invasion, and poorer prognosis.…”