Objective: Parathyroid hormone-related protein (PTHrP) is a regulatory peptide that has been associated with normal fetal growth and differentiation as well as the regulation of fetal calcium. In a variety of cancers, PTHrP has been implicated in the humoral hypercalcemia of malignancy. Recently, we demonstrated that all prostatic adenocarcinomas express PTHrP. In the present study, the localization of PTHrP and its mRNA in nonmalignant prostate tissue was assessed.
Methods: Formalin-fixed, paraffin-embedded prostatic tissues from 23 patients were evaluated. Immunocytochemistry (ICC) was performed by the streptavidin-peroxidase enzyme conjugate method using a monoclonal antibody, 8B12, generated against fragment 1-34 of the amino-terminal end of PTHrP. Nonradioactive in situ hybridization was carried out using a digoxigenin labeled single-stranded cDNA probe complementary to the sequence coding for PTHrP(15-120).
Results: PTHrP immunoreactivity was observed in the cytosol of a few epithelial cells. Double labeling and serial section ICC with 8B12 and a monoclonal antibody to chromogranin A (a generic neuroendocrine [NE] marker) revealed that PTHrP was present in a subpopulation of prostatic NE cells. In situ hybridization of mirror image sections demonstrated positive signals in prostatic NE cells in complete accordance with the ICC findings.
Conclusions: The localization and production of PTHrP in prostatic NE cells suggest that this polypeptide may act in an endocrine-paracrine fashion involved in the prostatic growth and differentiation as well as the regulation of calcium in semen and seminal fluid.