Heparanase-1 expression is associated with the metastatic potential of breast cancer.

BACKGROUND

Metastasis of malignant breast cells is in part mediated through degradation of the extra-cellular matrix by proteolysis, enabling malignant cells to migrate through the surrounding stroma. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate (HS) moiety of proteoglycans, a component of the extracellular matrix and basement membrane.

METHODS

Fifty-one primary breast tumors, 13 lymph node metastases, 4 ductal carcinoma in situ, 7 benign, and 5 normal specimens were examined for HPR1 expression using immunohistochemical staining. The functional role of HPR1 expression was determined by examining HS deposition using immunofluorescence staining.

RESULTS

Sixteen of 30 breast carcinomas (53%) with sentinel node metastasis expressed HPR1. In contrast, only 5 of 21 nonmetastatic primary breast carcinomas (23%) were HPR1 positive. Eighteen of 30 breast carcinomas between 1 and 5 cm expressed HPR1, compared with 3 of 21 HPR1-positive specimens in tumors < or =1 cm. Statistical analysis revealed that HPR1 expression was associated with breast tumor metastases (P =.04) and primary tumors between 1 and 5 cm (P =.002). Ninety percent of HPR1-positive tumors lacked HS deposition, suggesting an inverse correlation between HPR1 expression and HS deposition.

CONCLUSIONS

HPR1 expression correlates with the lack of HS deposition and with the metastatic potential of breast cancers. The frequency of HPR1 is significantly higher in breast tumors between 1 and 5 cm than in tumors < or =1 cm.