POLYMERASE CHAIN-REACTION ANALYSIS OF PARATHYROID HORMONE-RELATED PROTEIN GENE-EXPRESSION IN BREAST-CANCER PATIENTS AND OCCURRENCE OF BONE METASTASES

Parathyroid hormone-related protein (PTHrP) is associated with the syn drome of humoral hypercalcemia of malignancy. A high incidence of posi tive staining for PTHrP is observed in breast cancer and positivity is more frequent in patients who develop bone metastases. We assessed th e presence of PTHrP mRNA by using the polymerase chain reaction in 38 normocalcemic breast cancer patients with long-term follow-up (minimum , 5 years) selected for the presence or absence of later bone metastas is development. In all the patients except one, the PTHrP gene was exp ressed in the breast tumor. The level of amplified PTHrP complementary DNA was inversely related to age (P < 0.02) and positively related to the proportion of invaded nodes (P < 0.02) but was not related to the other usual prognostic factors. The level of PTHrP mRNA was not diffe rent between the group of patients without recurrence or metastases (n = 11) and the group of patients who later developed metastases in sof t tissues (n = 10). By contrast, patients who subsequently developed b one metastases (n = 17) showed higher PTHrP gene expression than patie nts in the other two groups (P < 0.001). This study suggests that stro ng PTHrP gene expression in breast tumors is associated with the onset of bone metastases.