Heparanase expression is an independent prognostic factor in patients with invasive cervical cancer

Abstract

Background: Endoglycosidic heparanase degrades heparan sulfate glycosaminoglycans, and may be important in cancer invasion and metastasis, although its expression in human cervical cancer has not been characterized. Materials and methods: Heparanase association with clinicopathological features related to prognostic significance was examined in patients presenting with invasive cervical cancer. Gene expression of heparanase was assessed by RT-PCR in 10 normal cervix and 92 invasive cervical cancer samples. Results: Heparanase mRNA expression was not detected in any of the normal cervix specimens, but was significantly higher in advanced-stage tumors (P = 0.026). In cases treated with radical hysterectomy and pelvic lymphadenectomy, heparanase mRNA expression was significantly higher in tumors exhibiting lymph-vascular space invasion (P = 0.01). A significant relationship was found between microvessel counts and heparanase mRNA expression (P = 0.035). The disease-free and overall survival rates of patients exhibiting heparanase mRNA expression were significantly lower than those of patients lacking heparanase mRNA expression (P = 0.019 and 0.017, respectively). Furthermore, multivariate analysis showed that heparanase mRNA expression was an independent prognostic factor for both disease-free and overall survival. Conclusions: These findings provide evidence that heparanase expression can serve as an indicator of aggressive potential and poor prognosis in cervical cancer. Consequently, heparanase inhibitor will be a novel candidate for therapeutic intervention in this disease.