Thrombospondin-1 and -2 Expressions in Hepatocellular Carcinomas: an Association with Tumor Angiogenesis and p53 Overexpression

ABSTRACT

Background: It has been suggested that thrombospondin (TSP) is a p53-dependent negative regulator of tumor angiogenesis. TSP expression and localization in hepatocellular carcinomas (HCCs) and its association with overexpression of p53 protein were investigated. Methods: TSP-1 and -2 expressions were examined in 40 HCC specimens by immunohistochemical staining and in 4 HCC cell lines by Western blotting. In addition, p53 protein expression and microvessel density (MVD) were correlated with the TSP expression. Results: Strong immu- nopositivity for TSP-1 was observed in fibroblasts, vascular endothelial cells, and some vas- cular smooth muscle cells of the stroma in 18 cases (45%), and in tumor cells in 3 cases (7.5%) of 40 cases of HCC. Immunoreactivity for TSP-2 was observed in only the sinusoidal lining cells of the tumor in 15 cases (46%), and in tumor cells in 2 cases (6%) of 32 cases of HCC. TSP-1 expression was inversely correlated with MVD (p=0.028), but TSP-2 expression did not show any correlation with MVD. Although p53 was overexpressed in 17 cases, there was no significant correlation between TSP and p53 expressions. None of the HCC cell lines expressed TSP-1 or -2. Conclusions: These findings indicate that TSP-1 is mainly derived from nonparenchymal cells, and may decrease tumor angiogenesis in HCC.