title: Secretagogin is a novel marker for neuroendocrine differentiation.
abstract: Our previous microarray-based studies identified secretagogin to be highly expressed in normal colon mucosa compared to basal expression in colon adenocarcinomas. The aim of this study was to analyze the differential expression of secretagogin in normal mucosa, adenocarcinomas, and neuroendocrine tumors. Western blotting, immunohistochemistry, immunofluorescence microscopy and ELISA were applied. Western blot analysis detected a 32-kDa secretagogin band in samples from normal mucosa. Immunohistochemical analyses on tissue specimens showed that secretagogin is exclusively expressed in neuroendocrine cells and nerve cells in normal mucosa of the digestive tract. Tissues adjacent to benign hyperplasic polyps and adenomas showed a decreased number of secretagogin-expressing neuroendocrine cells. Secretagogin co-localized with neuroendocrine markers (chromogranin A, neuron-specific enolase, synaptophysin) in neuroendocrine cells in crypts of normal mucosa, and in tumor cells of carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of 19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as well as in neuroendocrine tumors from the lung, pancreas and adrenal gland. Secretagogin was detected in plasma from carcinoid patients with distant metastasis. Combined immunohistochemical analysis of secretagogin and FK506-binding protein 65, a protein de novo synthesized in adenocarcinomas, distinguished well-differentiated carcinoids, adenocarcinoids and undifferentiated carcinomas. We conclude that secretagogin is a novel marker for neuroendocrine differentiation.
authors.affiliation: Molecular Diagnostic Laboratory, Center for Molecular Clinical Cancer Research, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby Sygehus, Aarhus, Denmark. kbdr@ki.au.dk
authors.forename: Karin
authors.initials: K
authors.lastname: Birkenkamp-Demtröder
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wagner
authors.forename: Flemming
authors.initials: F
authors.lastname: Brandt Sørensen
authors.forename: Lone
authors.initials: L
authors.lastname: Bording Astrup
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gartner
authors.forename: Hans
authors.initials: H
authors.lastname: Scherübl
authors.forename: Bernhard
authors.initials: B
authors.lastname: Heine
authors.forename: Peer
authors.initials: P
authors.lastname: Christiansen
authors.forename: Torben Falck
authors.initials: TF
authors.lastname: Ørntoft
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D064046:Secretagogins; D016708:Synaptophysin / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D053379:Chromogranin A; D002864:Chromogranins; C576556:SCGN protein, human; D064046:Secretagogins; D016708:Synaptophysin; D010751:Phosphopyruvate Hydratase; D022021:Tacrolimus Binding Proteins; C110054:FKBP10 protein, human; D019696:Peptidylprolyl Isomerase