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


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.
D000328:Adult; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000032:analysis / Q000096:biosynthesis*; D019812:Heparan Sulfate Proteoglycans; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000473:pathology* / Q000601:surgery
D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger; D005966:Glucuronidase