Research Papers:

Prognostic significance of heparanase expression in primary and metastatic breast carcinoma

Olga Vornicova, Inna Naroditsky, Ilanit Boyango, Shlomit S. Shachar, Tanya Mashiach, Neta Ilan, Israel Vlodavsky and Gil Bar-Sela _

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Oncotarget. 2018; 9:6238-6244. https://doi.org/10.18632/oncotarget.23560

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Olga Vornicova1, Inna Naroditsky2, Ilanit Boyango3, Shlomit S. Shachar1, Tanya Mashiach4, Neta Ilan3, Israel Vlodavsky3 and Gil Bar-Sela1

1Division of Oncology, Rambam Health Care Campus, Haifa, Israel

2Departments of Pathology, Rambam Health Care Campus, Haifa, Israel

3Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

4Statistics, Rambam Health Care Campus, Haifa, Israel

Correspondence to:

Gil Bar-Sela, email: [email protected]

Israel Vlodavsky, email: [email protected]

Keywords: heparanase; breast carcinoma; metastasis; survival; discordance

Received: September 27, 2017     Accepted: November 26, 2017     Published: December 21, 2017


High levels of heparanase are detected in many types of tumors, associated with bad prognosis. Typically, heparanase levels are evaluated in a biopsy taken from the primary lesion, whereas its expression by the resulting metastases is most often unresolved. This becomes critically important as anti-heparanase compounds enter advanced clinical trials. Here, we examined the expression of heparanase in pairs of primary and the resulting distant metastases of breast carcinoma. Interestingly, we found that heparanase expression in the metastatic lesion does not always reflect its expression in the primary tumor. Accordingly, in some cases, the primary lesion was stained positive for heparanase while the metastasis stained negative, and vice versa. Heparanase discordance occurred in 38% of the patients, higher than that reported for hormone receptors, and was associated with bad prognosis. Thus, examination of heparanase levels in the tumor metastases should be evaluated for most efficient precision medicine applying heparanase inhibitors. Furthermore, we found that in stage I breast cancer patients strong heparanase staining is associated with shorter overall survival. Thus, heparanase levels can assist in the diagnosis and in determining the necessity and type of treatment in early stage breast cancer.

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