Heparanase expression in gallbladder carcinoma and its correlation to prognosis.

OBJECTIVE

Heparanase is an endo-beta-glucuronidase that cleaves heparan sulfate and has been implicated in tumor angiogenesis and metastasis. The present study was to analyze the expression of and explore the prognostic value of heparanase and two important transcriptional factors, namely hypoxia-inducible factor-1alpha (HIF-1alpha) and nuclear transcriptional factor kappa B p65 (NF-kappaB p65) in gallbladder cancer.

METHODS

Heparanase, HIF-1alpha and NF-kappaB p65 protein levels in 38 patients with gallbladder carcinoma were detected by immunohistochemistry and analyzed for clinicopathological significance.

RESULTS

The heparanase, HIF-1alpha and NF-kappaB p65 proteins were found in 24 (63.2%), 13 (34.2%) and 22 (57.9%) specimens, respectively. High heparanase expression was closely related to advanced TNM stage (P = 0.007), depth of tumor invasion (P = 0.016), lymph node metastasis (P = 0.040) and decreased postoperative survival at 3 years (50.0% vs 20.8%, P = 0.001). Both HIF-1alpha and NF-kappaB p65 proteins were correlated with tumor size (P = 0.039 and P = 0.027, respectively) and patients positive for HIF-1alpha expression had a decreased survival rate compared with those negative for HIF-1alpha expression (40.0% vs 15.4%, P = 0.035). In addition, heparanase-positive cases had high expression of NF-kappaB p65 compared with the heparanase-negative cases (P = 0.047).

CONCLUSIONS

Heparanase and HIF-1alpha are frequently expressed in gallbladder carcinoma and are associated with decreased survival. High expression of heparanase, combined with NF-kappaB p65, may contribute to the highly invasive and metastatic behavior of gallbladder carcinoma.