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Annals of Oncology 14:1505-1510, 2003
© 2003 European Society for Medical Oncology

Original Paper

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

Y. Shinyo, J. Kodama+, A. Hongo, M. Yoshinouchi and Y. Hiramatsu

Department of Obstetrics and Gynecology, Okayama University Medical School, Okayama, Japan

Received 13 March 2003; revised 24 May 2003; accepted 4 June 2003

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.

Key words: angiogenesis, cervical cancer, heparanase, survival


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