127 DIFFERENTIAL EXPRESSION OF RANKL AND OSTEOPROTEGERIN IN PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CANCER
2011-04-01

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011127 DIFFERENTIAL EXPRESSION OF RANKL AND OSTEOPROTEGERIN IN PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CANCER Tilman Todenhoefer, Joerg Hennenlotter, Andrea Hohneder, Ursula Kuehs, David Schilling, Stefan Aufderklamm, Saladin Alloussi, Georgios Gakis, Arnulf Stenzl, and Christian Schwentner Tilman TodenhoeferTilman Todenhoefer Tuebingen, Germany , Joerg HennenlotterJoerg Hennenlotter Tuebingen, Germany , Andrea HohnederAndrea Hohneder Tuebingen, Germany , Ursula KuehsUrsula Kuehs Tuebingen, Germany , David SchillingDavid Schilling Tuebingen, Germany , Stefan AufderklammStefan Aufderklamm Tuebingen, Germany , Saladin AlloussiSaladin Alloussi Tuebingen, Germany , Georgios GakisGeorgios Gakis Tuebingen, Germany , Arnulf StenzlArnulf Stenzl Tuebingen, Germany , and Christian SchwentnerChristian Schwentner Tuebingen, Germany View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.194AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The receptor activator of NFkappaB Ligand (RANKL) pathway mediates interactions of tumor cells and bone microenvironment. RANKL is secreted by osteoblasts and bone marrow stromal cells and promotes osteolysis and development of bone metastases via activation of the RANK receptor on osteoclasts RANKL and osteoprotegerin (OPG) are also expressed by tumor cells. Our aim was to determine, if changes of RANKL and OPG are notable in the serum and bone marrow of patients with clinically localized prostate cancer (PC) without manifest bone metastases. METHODS Concentrations of total sRANKL (free and OPG-bound soluble RANKL) and OPG were determined in serum and bone marrow specimens of 20 patients undergoing radical prostatectomy for localized PC (Median Gleason score 7, Median PSA value 5,98 ng/ml, Median Age 66,5) and 9 individuals without PC (benign prostate hyperplasia or stone disease, Median Age 64,0) by Enzyme linked immunosorbent assay. Ratios of sRANKL/OPG were calculated. Disseminated tumor cells (DTC) in bone marrow were determined by cytokeratine immunocytochemistry. Values were compared and correlated to clinical data using the Wilcoxon-Kruskall-Wallis tests and linear regression analyses. RESULTS Median values of serum sRANKL, OPG and ratio for PC and non-PC patients were 33515, 62, 840 and 131, 63, 2 (p=0.015, 0.81 and 0.030), respectively. Serum and corresponding bone marrow values of all 3 investigated parameters correlated significantly (p<0.0001, p= 0,001 and p=0,008 for sRANKL, OPG and ratio, respectively). Concentrations of sRANKL and OPG in bone marrow and serum were independent from Gleason score and PSA value. Interestingly, patients with locally advanced prostate cancer (>pT2) showed lower serum sRANKL levels than those with organ-confined disease (p=0.04). The presence of DTCs did not significantly affect sRANKL and OPG in bone marrow and serum. CONCLUSIONS This is the first study analyzing sRANKL/OPG in bone marrow and corresponding serum of PC patients. Increased activity of RANKL with an elevated sRANKL/OPG ratio indicates osteolytic activity in these patients before bone metastases manifestation. As concentrations of total sRANKL and OPG in bone marrow and serum correlate significantly, measurement of sRANKL and OPG in serum reliably reflects the status of sRANKL/OPG in the bone marrow. These alterations are even notable in the absence of DTCs. These preliminary results give new insights in tumor-induced changes of RANKL activity and implicate a potential benefit of RANKL inhibition for patients with clinically localized PC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e53 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tilman Todenhoefer Tuebingen, Germany More articles by this author Joerg Hennenlotter Tuebingen, Germany More articles by this author Andrea Hohneder Tuebingen, Germany More articles by this author Ursula Kuehs Tuebingen, Germany More articles by this author David Schilling Tuebingen, Germany More articles by this author Stefan Aufderklamm Tuebingen, Germany More articles by this author Saladin Alloussi Tuebingen, Germany More articles by this author Georgios Gakis Tuebingen, Germany More articles by this author Arnulf Stenzl Tuebingen, Germany More articles by this author Christian Schwentner Tuebingen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...