Expression of Bone Sialoprotein in Primary Human Breast Cancer Is Associated with Poor Survival

We have recently demonstrated that bone sialoprotein (BSP), a bone-matrix protein involved in hydroxyapatite crystal formation, is ectopically expressed in human breast cancers. We explored a possible association between expression of BSP in primary breast cancer and patients' survival. We analyzed BSP expression in 454 breast-cancer patients by immunohistochemistry on archival paraffin-embedded material using an anti-BSP polyclonal antibody. BSP expression was correlated to survival, tumor size, axillary lymph-node status and first site of distant metastasis. Of the breast cancers analyzed, 89% expressed detectable amounts of BSP. We found a statistical association between expression of BSP and poor prognosis as indicated by survival curves analyzed using the log rank and the Gehan methods. BSP expression was significantly higher in breast-cancer patients with axillary lymph-node involvement. Interestingly, survival of patients with positive lymph nodes but BSP-negative tumors was significantly higher than that of patients with no lymph-node involvement but BSP-positive cancers. The frequency of bone metastases was higher in the group of patients with BSP-positive tumors (22%) than in the group with BSP-negative cancers (7%). There was a significant increase in the incidence of lung metastases in patients whose tumors were negative for BSP. Our data show that bone sialoprotein expression in breast cancer is associated with poor prognosis. BSP detection also appears to be a valuable marker with which to identify, among the lymph-node-negative patients, those who have high risk of disease progression.