The Role of Thymidine Phosphorylase and Thrombospondin-1 in Angiogenesis and Progression of Intrahepatic Cholangiocarcinoma

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Abstract
Thymidine phosphorylase (TP), an important regulator of angiogenesis, is correlated with progression, metastasis, and prognosis in various types of tumor. In contrast, both positive and negative effects of thrombospondin-1 (TSP-1) on angiogenesis have been reported. In the present study, we examined the expression of TP and TSP-1 in carci noma cells in 67 primary intrahepatic cholangiocarcinomas (ICCs) immunohistochem ically and its correlation with angiogenesis, clinicopathological features, and prognosis. Ttwenty-six (38.8%) cases were classified as exhibiting positive TP expression. TP ex pression showed a significant correlation with vascular invasion, lymphatic perme ation, perineural invasion, and lymph node metastasis. Thirty-four (50.7%) cases were classified as exhibiting positive TSP-1 expression. TSP-1 expression was significantly correlated with only lymphatic permeation. The microvessel count in positive TP ex pression cases was significantly higher than that in negative cases. In contrast, the mi crovessel count in negative TSP-1 expression cases was significantly higher than that in positive cases. Survival in patients who were positive for both TP and TSP-1 expression was significantly poor. Our results suggest that the increased TP expression and de creased TSP-1 expression contribute to angiogenesis, but that the role of angiogenesis in ICC is not closely related to tumor aggressiveness. The TP and TSP-1 expression in ICC may enhance tumor aggressiveness. Int J Surg Pathol 10(1):47-56, 2002