EXPRESSION OF THE RECEPTOR FOR PARATHYROID HORMONE-RELATED PROTEIN INNORMAL AND MALIGNANT BREAST-TISSUE

Parathyroid hormone-related protein (PTHrP) is the cause of humoral hy percalcaemia of malignancy and interacts with parathyroid hormone (PTH ) receptors, Breast cancer cells produce PTHrP in vitro and in vivo. T he breast cancer cell line MCF-7, which products PTHrP and expresses P THrP, receptors, proliferates in response to PTHrP. The aim of these s tudies was to determine the tissue location of PTHrP/PTH receptors (PT HrPR) in primary breast carcinomas and to establish whether they had t he potential to respond to PTHrP. The cellular location of mRNA for th e PTHrP/PTH receptor was identified using in situ hybridization in pri mary breast carcinomas and normal breast tissue, Immunohistochemistry for PTHrP was carried out on the same specimens, Tumours were assessed and scored by two observers using the product of intensity of signal and number of positive tumour cells (possible range 0-9). Tumours were also assessed for Ki-67 expression by counting positive nuclei, Non-m alignant ductular epithelium expressed mRNA for the PTHrP receptor (me an score 2.6, range 1-4). Breast carcinomas (mean score 4.4, range 0-9 ) showed variable expression of PTHrP, receptor mRNA: eight tumours we re negative, 50 had scores similar to normal breast tissue, and 49 had higher scores for the receptor, Levels of expression of the receptor within the primary breast carcinomas were unrelated to immunohistochem ical detection of PTHrP or to any standard prognostic factor, There wa s a significant (P=0.05) relationship between Ki-67 and PTHrPR express ion in individual tumours, The presence of PTHrP and its receptor in n ormal breast epithelium and breast carcinomas demonstrates that most b reast tumours are able to respond to PTHrP. The Ki-67 data suggest tha t PTHrP is a potential autocrine growth factor in primary breast carci noma. (C) 1997 John Wiley & Sons, Ltd.