Osteoprotegerin and rank ligand expression in prostate cancer

Objectives. To investigate the expression of osteoprotegerin (OPG) and RANK ligand (RANKL) in human prostatic tissues. The factors regulating the incr eased turnover associated with prostate cancer (CaP) bone metastasis are un known. OPC and RANKL are recently identified regulators of bone resorption and bone remodeling. Methods. Tissues from 28 patients with CaP and from 4 normal organ donors w ere analyzed by reverse transcriptase-polymerase chain reaction and immunoh istochemistry for the expression of OPC and RANKL. Results. OPG and RANKL messages were detected in both normal and cancerous prostate samples. In the normal prostate, OPG protein was detected in lumin al epithelial and stromal cells (5% to 65% and 15% to 70%, respectively) an d RANKL immunoreactivity was observed in 15% to 50% of basal epithelial cel ls, 40% to 90% of luminal epithelial cells, and 70% to 100% of stromal cell s. OPG was not detected in 8 of 10 primary CaP specimens; RANKL was heterog eneously expressed in 10 of 11 CaP specimens. The percentage of tumor cells expressing OPG and RANKL was significantly increased in all CaP bone metas tases compared with nonosseous metastases or primary CaP. Conclusions. CaP bone metastases were consistently immunoreactive for both OPG and RANKL compared with nonosseous metastases or primary CaP. The prese nce of these crucial bone resorption regulators in CaP bone metastases sugg ests a mechanism whereby CaP cells may modulate bone turnover and has profo und implications for the establishment and development of CaP bone metastas es in advanced disease. UROLOGY 57: 611-616, 2001. (C) 2001, Elsevier Scien ce Inc.