AbstractOBJECTIVECell membrane antigens like the gastrin‐releasing peptide receptor (GRPR), the prostate stem cell antigen (PSCA), and the prostate‐specific membrane antigen (PSMA), expressed in prostate cancer, are attractive targets for new therapeutic and diagnostic applications. Therefore, we investigated in this study whether these antigens are expressed in metastasized prostate cancer.METHODSFormalin‐fixed, paraffin‐embedded specimens of 15 patients with uni‐ or bilateral lymph node metastases of prostate cancer (totaling 21 cases) and 17 patient‐cases of bone metastases were processed for immunohistochemistry with anti‐GRPR, anti‐PSCA, and anti‐PSMA antibodies. A pathologist blinded to clinical and pathological data scored the immunoreactivity for these antibodies on a four‐point scale (0 = no staining; 1+ = weak staining; 2+ = moderate staining; 3+ = strong staining) and documented the distribution pattern.RESULTSGRPR staining in lymph node metastases was seen in 85.7% of cases (18 of 21 cases), PSCA in 95.2% (20/21), and PSMA in 100% (21/21). GRPR in bone metastases was seen in 52.9% of cases (9/17), PSCA in 94.1% (16/17), and PSMA in 100% (17/17).CONCLUSIONWe have shown for the first time that GRPR is expressed in the vast majority of lymph node metastases and in 52.9% of bone metastases of prostate cancer. PSCA and PSMA are both highly expressed in lymph node and bone metastases. Although PSCA and PSMA are mostly expressed in prostate cancer metastases, GRPR offers an interesting alternative target as it can be targeted relatively easy with peptide‐based (radio)pharmaceuticals. Prostate 69:1101–1108, 2009. © 2009 Wiley‐Liss, Inc.