The Prostate 67:472^ 484 (2007) Secretagogin is a New Neuroendocrine Marker in the Human Prostate Katja Adolf, 1 Ludwig Wagner, 2 Anders Bergh, 3 Pa ¨r Stattin, 4 Peter Ottosen, 5 Michael Borre, 6 Karin Birkenkamp-Demtro ¨ der, 1 Torben Falck Ørntoft, 1 and Niels Tørring 1 * 1 Molecular Diagnostic Laboratory, Department of Clinical Biochemistry,Center for Molecular Clinical Cancer Research (CMCC), Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej, A ‡ rhus, Denmark 2 Department of Medicine III, Division of Clinical Endocrinology and Metabolism,University of Vienna, Wa« hringer Gu« rtel,Vienna, Austria 3 Department of Medical Biosciences, Pathology,UmeÔ University Hospital,UmeÔ, Denmark 4 Department of Surgery and Perioperative Sciences,Urology and Andrology,UmeÔ University Hospital,UmeÔ, Sweden 5 Institute of Pathology, A ‡ rhus University Hospital, NÖrrebrogade, A ‡ rhus, Sweden 6 Department of Urology, Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej, A ‡ rhus, Denmark BACKGROUND. Neuroendocrine (NE) differentiation in prostate cancer (PCa), promoted by NE cell secreted products, appears to be associated with tumor progression, poor prognosis, and hormone-refractory disease. We recently reported secretagogin, a hexa-EF-hand Ca 2þ binding protein, as a novel NE marker in carcinoid tumors of the lung and the gastrointestinal tract. The present study analyzes the expression of secretagogin in normal and malign prostate tissue. METHODS. We analyzed immunoreactivity for secretagogin, chromogranin A (CgA), neuron specific enolase (NSE), and synaptophysin (SYN) in consecutive sections from 87 formalin-fixed paraffin-embedded (FFPE) benign hyperplastic (n ¼ 10) and prostate adenocarcinoma (n ¼ 77) specimens. The intracellular distribution of secretagogin, CgA, and NSE was examined by confocal fluorescent microscopy, and we characterized secretagogin in eight samples by Western blotting. RESULTS. Secretagogin is cytoplasmic and nuclear expressed in NE and NE differentiated cells, and to a lesser extent in epithelial cells, in the benign prostate and prostate adenocarcinoma cells. Secretagogin stained 82% (46/56) of benign and 71% (48/68) of prostate adenocarcinomas and co-localized with the NE markers CgA and NSE. The expression of secretagogin is significantly correlated to CgA (P < 0.001) and NSE (P < 0.048) in prostate adenocarcinoma and to CgA in normal epithelium (P < 0.028). Abbreviations: SCGN, secretagogin gene; CgA, chromogranin A; SYN, synaptophysin; NSE, neuron specific enolase; CKH, cytoker- atin high molecular weight; NE, neuroendocrine; NED, neuroendo- crine development; FFPE, formalin-fixed paraffin-embedded; PCa, prostate cancer; BPH, benign prostatic hyperplasia; IHC, immuno- histochemistry; HRPC, hormone-refractory prostate cancer; TNM, tumor nodes metastases; CNS, central nervous system; ELISA, enzyme-linked immmunosorbent assay; TUR-P, transurethral resec- tion of the prostate; HRP, horseradish peroxidase; DAB, 3,30- diaminobenzidine tetrahydrochloride; DAPI, 4 0 ,6-diamidino-2-phe- nylindole; RT, room temperature; TBS, tris-buffered saline; DTT, dithiothreitol; SDS–PAGE, sodium dodecylsulfate polyacrylamide gel electrophoresis; NP40, Nonidet P40; BSA, bovine serum albumin, HBSS, Hanks’ balanced salt solution. Grant sponsor: The John and Birthe Meyer Foundation; Grant sponsor: The Danish Cancer Society; Grant sponsor: Aarhus University; Grant sponsor: Aarhus County. *Correspondence to: Niels Tørring, PhD, Molecular Diagnostic Laboratory (MDL), Department of Clinical Biochemistry, Center for Molecular Clinical Cancer Research (CMCC), Aarhus University Hospital Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. E-mail: nto@ki.au.dk Received 7 July 2006; Accepted 29 August 2006 DOI 10.1002/pros.20523 Published online 6 February 2007 in Wiley InterScience (www.interscience.wiley.com). ß 2007 Wiley-Liss, Inc.