Parathyroid hormone-related protein (PTHrp) expression in human bone metastases (BM)

Abstract

9696 Background: Substantial animal data support a major role for PTHrp in tumor induced osteolysis. However, the presence of PTHrp in BM in humans has not yet been established. The purpose of this study was to determine the presence and frequency of PTHrp expression in BM from different types of cancer. Methods: Bone pathologic fractures or BM biopsies from 64 patients, median age 63 (36–85), 36 female, were analysed. Thirty-two had breast carcinoma, 10-gastrointestinal, 6-lung, 6-prostate, and 10 several other types of cancer. The lesions were lytic in 48 patients, blastic in 10 and mixed in 6. Nineteen patients had pathologic fractures (PF). Formalin fixed, decalcified, paraffin embedded sections of metastatic lesions were stained by an immunohistochemical (IHC) method using a mouse monoclonal antibody (Chugai Pharmaceutical Co., Ltd.) to human PTHrp. The expression of PTHrp in cancer cells was graded according to the percentage of stained cells (0; 1: < 25%; 2: 25–75%; 3: > 75%) and the intensity of staining (1, 2 or 3). A final IHC score (0–9) was obtained for each patient. The Mann-Whitney test and the Kruskal-Wallis test were employed to analyse the correlation among clinical factors and the IHC score. Results: 56/64 (87.5%) of patients showed PTHrp expression in the cancer cells in bone. There was no statistically significant difference in PTHrp expression regarding the primary tumor site (breast versus non-breast; p= 0.22), the x-ray pattern of BM (lytic versus blastic, or mixed lesions, p=0.85), or ER/PR expression in breast cancer cells in bone (p= 0.35). There was a statistically significant difference in PTHrp expression in patients who had PF (median score= 6) compared to patients without PF (median score=2.5), p=0.0007. Conclusions: The expression of PTHrp in BM was high and independent of the primary tumor origin or the x-ray pattern of the bone lesions. PTHrp expression was significantly higher in patients who had PF. This study suggests that therapies targeting PTHrp to treat BM should be tried in different types of cancer and may be useful to prevent PF. No significant financial relationships to disclose.