Heparanase is overexpressed in lung cancer and correlates inversely with patient survival.
BACKGROUND
Heparanase is an endo-beta-D-glucuronidase that is capable of cleaving heparan sulfate (HS) side chains at a limited number of sites, yielding HS fragments of still appreciable size (approximately 5-7 kDa). Heparanase activity has been detected frequently in several cell types and tissues. Heparanase activity correlates with the metastatic potential of tumor-derived cells, a correlation that has been attributed to enhanced cell dissemination as a consequence of HS cleavage and remodeling of the extracellular matrix barrier.


METHODS
In this study, the authors examined heparanase expression in 114 patients with lung cancer by means of immunohistochemistry and correlated clinical-pathologic data with heparanase immunostaining and cellular localization.


RESULTS
Heparanase was overexpressed in 75% of the study patients. Heparanase expression was correlated with lung cancer lymph node status and metastasis classification (P = .04 and P = .01, respectively) and was correlated inversely with patient survival (P = .007). It is noteworthy that this adverse effect depended largely on the cellular localization of heparanase. Thus, whereas cytoplasmic staining of heparanase is associated with a poor prognosis, nuclear heparanase predicts a favorable outcome for patients with lung cancer.


CONCLUSIONS
The current findings suggest that heparanase expression and cellular localization are decisive for lung cancer patients' prognosis, most likely because of heparanase-mediated tumor cell dissemination by blood and lymph vessels.
Cohen
Esti
E
Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Doweck
Ilana
I
Naroditsky
Inna
I
Ben-Izhak
Ofer
O
Kremer
Ran
R
Best
Lael A
LA
Vlodavsky
Israel
I
Ilan
Neta
N
D000230:Adenocarcinoma / Q000201:enzymology*; D000368:Aged; D014408:Biomarkers, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D015996:Survival Rate; D000099175:Heparanase
D014408:Biomarkers, Tumor; D005966:Glucuronidase; D000099175:Heparanase