Expression of the calcium receptor in human breast cancer--a potential new marker predicting the risk of bone metastases

Abstract

Aims: This study investigates whether the calcium-sensing receptor (CaR) is commonly expressed in primary breast cancers. The CaR controls secretion of PTHrP in several breast cancer cell lines and PTHrP is known to stimulate osteolysis during metastatic bone resorption. Whether this could explain the propensity of breast cancers to develop bone metastases has not been explored.

Methods: With Ethical Committee approval, immunohistochemistry was performed using a commercially available antiCaR antibody (AffinityBioReagents, Cambridge, UK) on archived histological sections of primary tumours from patients who died with advanced breast cancer. Intensity of CaR expression was assessed by two independent observers on a 6-point scale.

Results: One hundred and eight patients with breast cancer were found to have positive bone scans, 42 patients had died. Of the patients with negative bone scans, 23 had liver or lung metastases. Most patients with strongly expressed CaR (score 4-5 on immunohistochemistry) had bone metastases (13/15 patients) compared with 2/23 patients with normal bone scans (p < 0.001, chi(2) test). Other clinical/pathological markers (ER, PR, c-erb B-2, LN status) were not significantly different between patients with CaR-positive or CaR-negative tumours.

Conclusions: CaR expression is common in a selected group of patients with advanced primary breast cancers. A prospective study should investigate if patients with CaR-positive tumours are more likely to develop bone metastases.