Expression of heparanase and hypoxia-inducible factor-1α in cholangiocarcinoma

Objective To detect the expressions of heparanase and hypoxia-inducible factor-1α(HIF-1α) in cholangiocarcinoma and analyze their relationship with prognosis and explore the possible mechanism of HIF-1α for regulation of heparanase.Methods Heparanase and HIF-1α proteins in the tumor and adjacent tissues were detected by immunohistochemistry in 48 patients with cholangiocarcinoma and analyzed their relationship with clinicopathological significance and prognosis.Results Heparanase and HIF-1α proteins were found in 30(62.5%) and 22(45.9%) tumor specimens,respectively,significantly higher than that in the adjacent tissues.High heparanase expression was closely correlated to advanced TNM stage(P=0.031),lymph node metastasis(P=0.003) and negatively correlated to 3-year postoperative survival(20.0% vs.0%,P=0.001).HIF-1α expression was associated with lymph node metastasis(P=0.017) and distant metastasis(P=0.031),but had a higher positive rate in heparanase-positive cases than in heparanase-negative cases(P=0.018).Multivariate analysis showed that neither heparanase nor HIF-1α was the independent prognostic factor.Conclusion Heparanase is overexpressed in cholangiocarcinoma in association with decreased postoperative survival.HIF-1α may up-regulate heparanase expression and promote heparanase-mediated tumor invasion and metastasis.