Expression of the calcium receptor in human breast cancer--a potential new marker predicting the risk of bone metastases.
OBJECTIVE
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.
Department os Surgery, University of Bristol, UK. r_mihai99@hotmail.com
R
R
Mihai
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J
Stevens
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C
McKinney
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NB
Ibrahim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000556:secondary; D002423:Cause of Death; D005260:Female; D005544:Forecasting; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D044169:Receptors, Calcium-Sensing / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D012307:Risk Factors
D014408:Biomarkers, Tumor; D044162:Parathyroid Hormone-Related Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D044169:Receptors, Calcium-Sensing; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone