Significance of the parathyroid hormone-related protein expression in breast carcinoma

Background: Parathyroid hormone-related protein (PTHrP) is produced by various neoplasms and is known to be a causative factor of hypercalcemia of malignancy. It has also been suggested to act as a cytokine for tumor progression. The purpose of this study was to clarify the significance of PTHrP expression in breast carcinoma. Methods: PTHrP expression was examined in 177 surgically resected breast carcinoma specimens by immunohistochemistry using a monoclonal antibody against the for PTHrP, The relationship of PTHrP expression with clinicopathological factors was analyzed and the clinical courses of the patients are reported. Results: Positive PTHrP staining was detected in 113 (64%) of the breast tumors. Among the positive cases, 36 (32%) of the tumors clearly showed strong expression. When the PTHrP expression was divided into three categories, a significant positive relationship was found be~een PTHrP expression and histological grade of tumor. PTHrP expression was also significantly related to bone metastasis but the staining degree of PTHrP was not. The patients with positive PTHrP tended to have poor outcome in proportion to the staining degree. Univariate analysis demonstrated a significantly shorter overall survival for patients expressing PTHrP, and in multivariate analysis showed that PTHrP status and nodal status were associated with a significantly shorter overall survival. Conclusion: Our results suggest that PTHrP expression is not only correlated with bone metastasis but is also related to the progression of breast carcinoma, and that overexpression of PTHrP may be a potential prognostic factor for human breast carcinoma.