Heparanase expression in gallbladder carcinoma and its correlation to prognosis

Abstract Background and Aim: Heparanase is an endo‐β‐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‐1α (HIF‐1α) and nuclear transcriptional factor kappa B p65 (NF‐κB p65) in gallbladder cancer. Methods: Heparanase, HIF‐1α and NF‐κB p65 protein levels in 38 patients with gallbladder carcinoma were detected by immunohistochemistry and analyzed for clinicopathological significance. Results: The heparanase, HIF‐1α and NF‐κB 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‐1α and NF‐κB p65 proteins were correlated with tumor size ( P = 0.039 and P = 0.027, respectively) and patients positive for HIF‐1α expression had a decreased survival rate compared with those negative for HIF‐1α expression (40.0% vs 15.4%, P = 0.035). In addition, heparanase‐positive cases had high expression of NF‐κB p65 compared with the heparanase‐negative cases ( P = 0.047). Conclusion: Heparanase and HIF‐1α are frequently expressed in gallbladder carcinoma and are associated with decreased survival. High expression of heparanase, combined with NF‐κB p65, may contribute to the highly invasive and metastatic behavior of gallbladder carcinoma.