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Synaptophysin and chromogranins/secretogranins widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis

Virchows Archiv B volume 58, pages 95–121 (1989)Cite this article

Summary

Normal and neoplastic neuroendocrine (NE) cells have been identified for many years by morphological criteria only. With the advent of immunocytochemistry, antibodies against NE-specific polypeptides have been used to identify NE cells that had been missed by conventional techniques, thus improving the diagnosis of NE cells. In this review article we discuss (i) the biochemical, cell biological and molecular biological data obtained so far for two major types of NE markers, synaptophysin, which is characteristic of the small “transparent-looking” neurosecretory vesicles, and the chromogranins/secretogranins, which are widespread constituents of the larger “dense-cored” secretory granules; (ii) the immunohistochemical data obtained for these marker proteins in normal and neoplastic human NE cells and tissues; and (iii) future possible developments involving these as well as other proteins that are associated with these two distinct secretory organelles of NE cells and may serve as potential markers in NE cell diagnosis.

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References

  • Abbs MT, Phillips JH (1980) Organisation of the proteins of the chromaffin granule membrane. Biochem Biophys Acta 595:200–221

    PubMed  CAS  Google Scholar 

  • Addis BJ, Hamid Q, Ibrahim NBN, Fahey M, Bloom SR, Polak JM (1987) Immunohistochemical markers of small cell carcinoma and related neuroendocrine tumours of the lung. J Pathol 153:137–150

    PubMed  CAS  Google Scholar 

  • Ahn TG, Cohn DV, Gorr SU, Ornstein DL, Kashdan MA, Levine MA (1987) Primary structure of bovine pituitary secretory protein I (chromogranin A) deduced from the cDNA sequence. Proc Natl Acad Sci USA 84:5043–5047

    PubMed  CAS  Google Scholar 

  • Apps DK, Percy JM (1987) The H +-translocating ATPase of chromaffin granule membranes. Ann NY Acad Sci 493:178–188

    PubMed  CAS  Google Scholar 

  • Azzopardi JG, Evans DJ, Krausz T (1986) Endocrine differentiation in breast tumours. Histopathology 10:773–774

    PubMed  CAS  Google Scholar 

  • Benedum UM, Baeuerle PA, Konecki DS, Frank R, Powell J, Mallet J, Huttner WB (1986) The primary structure of bovine chromogranin A: a representative of a class of acidic secretory proteins common to a variety of peptidergic cells. EMBO J 5:1495–1502

    PubMed  CAS  Google Scholar 

  • Benedum UM, Lamouroux A, Konecki DS, Rosa P, Hille A, Baeuerle PA, Frank R, Lottspeich F, Mallet J, Huttner WB (1987) The primary structure of human secretogranin I (chromogranin B): comparison with chromogranin A reveals homologous terminal domains and a large intervening variable region. EMBO J 6:1203–1211

    PubMed  CAS  Google Scholar 

  • Bishop AE, Polak JM, Facer P, Ferri G-L, Marangos PJ, Pearse AGE (1982) Neuron specific enolase: A common marker for the endocrine cells and innervation of the gut and pancreas. Gastroenterol 83:902–912

    CAS  Google Scholar 

  • Bishop AE, Pietroletti R, Taat CW, Brummelkamp WH, Polak JM (1987) Increased populations of endocrine cells in Crohn’s ileitis. Virchows Arch [A] 410:391–396

    CAS  Google Scholar 

  • Bishop AE, Bretherton-Watt D, Hamid QA, Fahey M, Shepherd N, Valentino K, Tatemoto K, Ghatei MA, Bloom SR, Polak JM (1988) The occurence of pancreastatin in tumours of the diffuse neuroendocrine system. Mol Cell Probes 2:225–235

    PubMed  CAS  Google Scholar 

  • Blaschko H, Comline RS, Schneider FH, Silver M, Smith AD (1967) Secretion of a chromaffin granule protein, chromogranin from the adrenal gland after splanchnic stimulation. Nature 215:58–59

    PubMed  CAS  Google Scholar 

  • Blomjous CEM, Thunnissen GBJM, Vos W, De Voogt HJ, Meijer CJLM (1988) Small cell neuroendocrine carcinoma of the urinary bladder. Virchows Archiv [A] 413:505–512

    CAS  Google Scholar 

  • Bordi C, Krisch K, Horvat G, Srikanta S (1988) Immunocytochemical patterns of islet cell tumors as defined by the monoclonal antibody HISL-19. Am J Pathol 132:249–257

    PubMed  CAS  Google Scholar 

  • Buckley K, Kelly RB (1985) Identification of a transmembrane glycoprotein specific for secretory vesicles of neural and endocrine cells. J Cell Biol 100:1284–1294

    PubMed  CAS  Google Scholar 

  • Buckley KM, Floor E, Kelly RB (1987) Cloning and sequence analysis of cDNA encoding p38, a major synaptic vesicle protein. J Cell Biol 105:2447–2456

    PubMed  CAS  Google Scholar 

  • Buffa R, Rindi G, Sessa F, Fini A, Capella C, Jahn R, Navone F, De Camilli P, Solcia E (1988) Synaptophysin immunoreactivity and small clear vesicles in neuroendocrine cells and related tumours. Mol Cell Probes 1:367–381

    Google Scholar 

  • Bussolati G, Gugliotta P, Sapino A, Eusebi V, Lloyd RV (1985) Chromogranin-reactive endocrine cells in argyrophilic carcinomas (“carcinoids”) and normal tissue of the breast. Am J Pathol 120:186–192

    PubMed  CAS  Google Scholar 

  • Bussolati G, Papotti M, Sapino A, Gugliotta P, Ghiringhello B, Azzopardi JG (1987) Endocrine markers in argyrophilic carcinomas of the breast. Am J Surg Pathol 11:248–256

    PubMed  CAS  Google Scholar 

  • Chejfec G, Falkmer S, Grimelius L, Jacobsson B, Rodensjo M, Wiedenmann B, Franke WW, Lee I, Gould VE (1987) Synaptophysin. A new marker for pancreatic neuroendocrine tumors. Am J Surg Pathol 11:241–247

    PubMed  CAS  Google Scholar 

  • Cohn DV, Zangerle R, Fischer-Colbrie R, Chu LLH, Elting JJ, Hamilton JW, Winkler H (1982) Similarity of secretory protein I from parathyroid gland to chromogranin A from adrenal medulla. Proc Natl Acad Sci USA 79:6056–6059

    PubMed  CAS  Google Scholar 

  • Cohn DV, Elting JJ, Frick M, Elde R (1984) Selective localization of the parathyroid secretory protein-I/adrenal medulla chromogranin A protein family in a wide variety of endocrine cells of the rat. Endocrinology 114:1963–1974

    PubMed  CAS  Google Scholar 

  • Cozzi MG, Zanini A (1988) Secretogranin II is a Ca2+-binding protein. Cell Biol Int Rep 12:493

    PubMed  CAS  Google Scholar 

  • Cozzi MG, Rosa P, Greco A, Hille A, Huttner WB, Zanini A, De Camilli P (1989) Immunohistochemical localization of secretogranin II in the rat cerebellum. Neuroscience 28:423–441

    PubMed  CAS  Google Scholar 

  • Davies AM, Bandtlow C, Heumann R, Korsching S, Rohrer H, Thoenen H (1987) Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature 326:353–358

    PubMed  CAS  Google Scholar 

  • Dayal Y, Kirsten A, Tallberg BS, Nunnemacher G, DeLellis RA, Wolfe HJ (1986) Duodenal carcinoids in patients with and without neurofibromatosis. Am J Surg Pathol 10:348–357

    PubMed  CAS  Google Scholar 

  • De Camilli P, Cameron R, Greengard P (1983a) Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections. J Cell Biol 95:1337–1354

    Google Scholar 

  • De Camilli P, Harris Jr SM, Huttner WB, Greengard P (1983b) Synapsin I (protein I), nerve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demon-117 strated by immunocytochemistry in agarose-embedded synaptosomes. J Cell Biol 96:1355–1373

    PubMed  Google Scholar 

  • De Camilli P, Vitadello M, Canevini MP, Zanoni R, Jahn R, Gorio A (1988) The synaptic vesicle proteins synapsin I and synaptophysin (protein P38) are concentrated both in efferent and afferent nerve endings of the skeletal muscle. J Neurosci 8:1625–1631

    PubMed  Google Scholar 

  • Deftos LJ, Murray SS, Burton DW, Partner RJ, O’Connor DT, Delageane AM, Mellon PL (1986) A cloned chromogranin A (CgA) cDNA detects of 2.3 Kb mRNA in diverse neuroendocrine tissues. Biochem Biophys Res Commun 29:418–423

    Google Scholar 

  • De Lellis RA, Dayal Y, Wolfe HJ (1984) Carcinoid tumors: changing concepts and new perspectives. Am J Surg Pathol 8:295–300

    Google Scholar 

  • DeStephano DB, Lloyd RV, Pike AM, Wilson BS (1984) Pituitary adenomas. An immunohistochemical study of hormone production and chromogranin localization. Am J Pathol 116:464–472

    PubMed  CAS  Google Scholar 

  • Ehrhart M, Grube D, Bader MF, Aunis D, Gratzl M (1986) Chromogranin A in the pancreatic islet: cellular and subcellular distribution. J Histochem Cytochem 34:1673–1682

    PubMed  CAS  Google Scholar 

  • Ehrhart M, Jorns A, Grube D, Gratzl M (1988) Cellular distribution and amount of chromogranin A in bovine endocrine pancreas. J Histochem Cytochem 36:467–472

    PubMed  CAS  Google Scholar 

  • Eiden LE (1987) Is chromogranin a prohormone? Nature 325:301

    PubMed  CAS  Google Scholar 

  • Eiden LE, Huttner WB, Mallet J, O’Connor DT, Winkler H, Zanini A (1987) A nomenclature proposal for the chromogranin/secretogranin proteins. Neuroscience 21:1019–1021

    PubMed  CAS  Google Scholar 

  • Facer P, Bishop AE, Lloyd RV, Wilson BS, Hennessy RJ, Polak JM (1985) Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract. Gastroenterology 89:1366–1373

    PubMed  CAS  Google Scholar 

  • Falkmer S, Hakanson R, Sundler F (1984) Evolution and tumor pathology of the neuroendocrine system. Elsevier, Amsterdam

    Google Scholar 

  • Fischer-Colbrie R, Schachinger M, Zangerle R, Winkler H (1982) Dopamine beta-hydroxylase and other glycoproteins from the soluble content and the membranes of adrenal chromaffin granules. Isolation and carbohydrate analysis. J Neurochem 38:725–732

    PubMed  CAS  Google Scholar 

  • Fischer-Colbrie R, Zangerle R, Frischenschlager I, Weber A, Winkler H (1984) Isolation and immunological characterization of a glycoprotein from adrenal chromaffin granules. J Neurochem 42:1008–1016

    PubMed  CAS  Google Scholar 

  • Fischer-Colbrie R, Lassmann H, Hagn C, Winkler H (1985) Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissues. Neuroscience 16:547–555

    PubMed  CAS  Google Scholar 

  • Fischer-Colbrie R, Hagn C, Schober M (1987) Chromogranins A, B, and C: widespread constituents of secretory vesicles. Ann NY Acad Sci 493:120–134

    PubMed  CAS  Google Scholar 

  • Fischer-Colbrie R, Iacangelo A, Eiden LE (1988) Neural and humoral factors separately regulate neuropeptide Y, enkephalin, and chromogranin A and B mRNA levels in rat adrenal medulla. Proc Natl Acad Sci USA 85:3240–3244

    PubMed  CAS  Google Scholar 

  • Forss-Petter S, Danielson P, Battenberg E, Bloom F, Sutcliffe GJ (1989) Nucleotide sequence and cellular distribution of rat chromogranin B (secretogranin I) mRNA in the neuroendocrine system. J Mol Neurosci 1:63–75

    PubMed  CAS  Google Scholar 

  • Franke WW, Grund C, Achtstätter T (1986) Co-expression of cytokeratins and neurofilament proteins in a permanent cell line: cultured rat PC12 cells combine neuronal and epithelial features. J Cell Biol 103:1933–1943

    PubMed  CAS  Google Scholar 

  • Gauweiler B, Weihe E, Hartschuh W, Yanaihara N (1988) Presence and coexistence of chromogranin A and multiple neuropeptides in Merkel cells of mammalian oral mucosa. Neurosci Lett 89:121–126

    PubMed  CAS  Google Scholar 

  • Gavine FS, Pryde JG, Deane DL, Apps DK (1984) Glycoproteins of the chromaffin granule membrane: separation by two-dimensional electrophoresis and identification by Lectin binding. J Neurochem 43:1243–1252

    PubMed  CAS  Google Scholar 

  • Gazdar AF, Helman LJ, Israel MA, Russell EK, Linnoila RI, Mulshine JL, Schuller HM, Park JG (1988) Expression of neuroendocrine cell markers L-dopa decarboxylase, chromogranin A, and dense core granules in human tumors of endocrine and nonendocrine origin. Cancer Res 48:4078–4082

    PubMed  CAS  Google Scholar 

  • Gerdes H-H, Phillips E, Huttner WB (1988) The primary structure of rat secretogranin II deduced from a cDNA sequence. Nucleic Acids Res 16:11811–11812

    PubMed  CAS  Google Scholar 

  • Gerdes H-H, Rosa P, Phillips E, Baeuerle PA, Frank R, Argos P, Huttner WB (1989) The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pHand calcium-induced aggregation. J Biol Chem 264:12009–12015

    PubMed  CAS  Google Scholar 

  • Gersell D, Mazonjian F, Mutch DG, Rindloff MA (1988) Undifferentiated carcinoma of the cervix. A cliniopathologic ultrastructural and immunocytochemical study of 15 cases. Am J Surg 12:684–699

    CAS  Google Scholar 

  • Gorr S-U, Dean WL, Radley TL, Cohn DV (1988) Calciumbinding and aggregation properties of parathyroid secretory protein-I (chromogranin A). Bone Mineral 4:17–25

    CAS  Google Scholar 

  • Gould VE, DeLellis RA (1983) The neuroendocrine system: Its tumors, hyperplasias, and dysplasias. In: Silverberg SG (ed) Principles and practice of surgical pathology. John Wiley & Sons Inc, New York, pp 1487–1501

    Google Scholar 

  • Gould VE, Wiedenmann B, Lee I, Schwechheimer K, Dockhorn-Dworniczak B (1987) Synaptophysin expression in neuroendocrine neoplasms as determined by immunocytochemistry. Am J Pathol 126:243–257

    PubMed  CAS  Google Scholar 

  • Grube D, Aunis D, Bader F, Cetin Y, Jorns A, Yoshie S (1986) Chromogranin A (CGA) in the gastro-entero-pancreatic (GEP) endocrine system. I. CGA in the mammalian endocrine pancreas. Histochemistry 85:441–452

    PubMed  CAS  Google Scholar 

  • Hagn C, Schmid KW, Fischer-Colbrie R, Winkler H (1986) Chromogranin A, B, and C in human adrenal medulla and endocrine tissues. Lab Invest 55:405–411

    PubMed  CAS  Google Scholar 

  • Haimoto H, Takahashi Y, Koshikawa T, Nagura H, Kato K (1985) Immunohistochemical localization of gamma-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab Invest 52:257–263

    PubMed  CAS  Google Scholar 

  • Hamid QA, Bishop AE, Sikri KL, Varndell IM, Bloom SR, Polak JM (1986) Immunocytochemical characterization of 10 pancreatic tumours, associated with the glucagonoma syndrome, using antibodies to separate regions of the proglucagon molecule and other neuroendocrine markers. Histopathology 10:119–133

    PubMed  CAS  Google Scholar 

  • Hartschuh W, Weihe E (1988) Multiple messenger candidates and marker substances in the mammalian Merkel cell — axon complex: a light and electron microscopic immunohistochemical study. Progress Brain Res 74:181–187

    CAS  Google Scholar 

  • Hashimoto S, Fumagalli G, Zanini A, Meldolesi J (1987) Sorting of three secretory proteins to distinct secretory granules in acidophilic cells of cow anterior putuitary. J Cell Biol 105:1579–1586

    PubMed  CAS  Google Scholar 

  • Hearn SA (1987) Electron microscopic localization of chromogranin A in osmium-fixed neuroendocrine cells with a protein A-gold technique. J Histochem Cytochem 35:795–801

    PubMed  CAS  Google Scholar 

  • Helle KB (1966) Some chemical and physical properties of the soluble protein fraction of bovine adrenal chromaffin granules. Mol Pharmacol 2:298–310

    PubMed  CAS  Google Scholar 

  • Helman LJ, Gazdar AF, Park JG, Cohen PS, Cotelingam JD, Israel MA (1988) Chromogranin A expression in normal and malignant human tissues. J Clin Invest 82:686–690

    PubMed  CAS  Google Scholar 

  • Helman LJ, Ahn TG, Levine MA, Allison A, Cohen PS, Cooper PS, Cooper MJ, Cohn DV, Israel MA (1988) Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA. J Biol Chem 263:11559–11563

    PubMed  CAS  Google Scholar 

  • Herbst WM, Kummer W, Hofmann W, Otto H, Heym C (1987) Carcinoid tumors of the thymus. An immunohistochemical study. Cancer 60:2465–2470

    PubMed  CAS  Google Scholar 

  • Hofmann WJ, Eberlein-Gonska M, Wiedenmann B, Otto HF (1989) Histochemische und immunhistologische Untersuchungen von 8 Thymuscarcinoiden mit neuroendokrinen Zellmarkern. Eine Untersuchung zur Evaluation unterschiedlicher diagnostischer Methoden an mediastinalen Carcinoiden. Verh Dtsch Ges Path 73 (in press)

  • Hogue-Angeletti R, Hickey WF (1985) A neuroendocrine marker in tissues of the immune system. Science 230:89–90

    Google Scholar 

  • Hoog A, Gould VE, Grimelius L, Franke WW, Falkmer S, Chejfec G (1988) Tissue fixation methods alter the immunohistochemical demonstrability of synaptophysin. Ultrastruct Pathol 12:673–678

    PubMed  CAS  Google Scholar 

  • Huttner WB, Lee RWH (1982) Protein sulfation on tyrosine residues. J Cell Biol 95:389a

    Google Scholar 

  • Huttner WB, Schiebler W, Greengard P, De Camilli P (1983) Synapsin I (protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation. J Cell Biol 96:1374–1388

    PubMed  CAS  Google Scholar 

  • Huttner WB, Benedum UM (1987) Chromogranin A and pancreastatin. Nature 325:305

    PubMed  CAS  Google Scholar 

  • Hutton JC, Davidson HW, Grimaldi KA, Peshavaria M (1987) Biosynthesis of betagranin in pancreatic beta-cells. Identification of a chromogranin A-like precursor and its parallel processing with proinsulin. Biochem J 244:449–456

    PubMed  CAS  Google Scholar 

  • Hutton JC, Peshavaria M, Johnston CF, Ravazzola M, Orci L (1988) Immunolocalization of Betagranin: A chromogranin A-related protein of the pancreatic B-cell. Endocrinology 122:1014–1020

    PubMed  CAS  Google Scholar 

  • Iacangelo A, Affolter HU, Eiden LE, Herbert E, Grimes M (1986) Bovine chromogranin A sequence and distribution of its messenger RNA in endocrine tissues. Nature 323:82–86

    PubMed  CAS  Google Scholar 

  • Iacangelo AL, Fischer-Colbrie R, Koller KJ, Brownstein MJ, Lee EE (1988) The sequence of porcine chromogranin a messenger RNA demonstrates chromogranin A can serve as the precursor for the biologically active hormone, pancreastatin. Endocrinology 122:2339–2342

    PubMed  CAS  Google Scholar 

  • Inoue M, DeLellis RA, Scully RE (1986) Immunohistochemical demonstration of chromogranin in endometrial carcinomas with argyrophil cells. Hum Pathol 17:841–847

    PubMed  CAS  Google Scholar 

  • Jahn R, Schiebler W, Ouimet C, Greengard P (1985) A 38000dalton membrane protein (p38) present in synaptic vesicles. Proc Natl Acad Sci USA 82:4137–4141

    PubMed  CAS  Google Scholar 

  • Johnson TI, Shapiro B, Beierwaltes WH, Orringer MB, Lloyd RV, Sisson JC (1985) Cardiac paragangliomas. A clinicopathologic and immunohistochemical study of four cases. Am J Surg Pathol 9:827–834

    PubMed  CAS  Google Scholar 

  • Johnson RG Jr (1987) Proton pumps and chemiosmotic coupling as a generalized mechanism of neurotransmitter and hormone transport. Ann NY Acad Sci 493:162–177

    PubMed  CAS  Google Scholar 

  • Kaufmann E, Geisler N, Weber K (1984) SDS-PAGE strongly overestimates the molecular masses of the neurofilament proteins. FEBS Lett 170:81–84

    PubMed  CAS  Google Scholar 

  • Kayser K, Schmid W, Ebert W, Wiedenmann B (1988) Expression of neuroendocrine markers (neuron-specific enolase, synaptophysin and bombesin) in carcinoma of the lung. Pathol Res Pract 183:412–417

    PubMed  CAS  Google Scholar 

  • Kemper B, Habener JF, Rich A, Potts JT Jr (1974) Parathyroid secretion: Discovery of a major calcium-dependent protein. Science 184:167–169

    PubMed  CAS  Google Scholar 

  • Kiang W-L, Krusius T, Finne J, Margolis RU, Margolis RK (1982) Glycoproteins and proteoglycans of the chromaffm granule matrix. J Biol Chem 257:1651–1659

    PubMed  CAS  Google Scholar 

  • Kimura N, Sasano N, Yamada R, Satoh J (1988) Immunohistochemical study of chromogranin in 100 cases of pheochromocytoma, carotid body tumour, medullary thyroid carcinoma and carcinoid tumour. Virchows Arch [A] 413:33–38

    CAS  Google Scholar 

  • Knaus P, Betz H, Rehm H (1986) Expression of synaptophysin during postnatal development of the mouse brain. J Neurochem 47:1302–1304

    PubMed  CAS  Google Scholar 

  • Konecki DS, Benedum UM, Gerdes HH, Huttner WB (1987) The primary structure of human chromogranin A and pancreastatin. J Biol Chem 262:17026–17030

    PubMed  CAS  Google Scholar 

  • Krisch K, Buxbaum P, Horvat G, Krisch I, Neuhold N, Ulrich W, Srikanta S (1986) Monoclonal antibody HISL-19 as an immunocytochemical probe for neuroendocrine differentiation. Its application in diagnostic pathology. Am J Pathol 123:100–108

    PubMed  CAS  Google Scholar 

  • Krisch K, Horvat G, Krisch I, Wengler G, Alibeik H, Neuhold N, Ulrich W, Braun O, Hochmeister M (1988) Immunochemical characterization of a novel secretory protein (defined by monoclonal antibody HISL-19) of peptide hormone producing cells which is distinct from chromogranin A, B, and C. Lab Invest 58:411–420

    PubMed  CAS  Google Scholar 

  • Lassmann H, Hagn C, Fischer-Colbrie R, Winkler H (1986) Presence of chromogranin A, B and C in bovine endocrine and nervous tissues: a comparative immunohistochemical study. Histochem J 18:380–386

    PubMed  CAS  Google Scholar 

  • Lauweryns JM, van Ranst K, Lloyd RV, O’Connor DT (1987) Chromogranin in bronchopulmonary neuroendocrine cells. Immunocytochemical detection in human, monkey, and pig respiratory mucosa. J Histochem Cytochem 35:113–118

    PubMed  CAS  Google Scholar 

  • Lee I, Gould VE, Moll R, Wiedenmann B, Franke WW (1987) Synaptophysin expressed in the bronchopulmonary tract: neuroendocrine cells, neuroepithelial bodies, and neuroendocrine neoplasms. Differentiation 34:115–125

    PubMed  CAS  Google Scholar 

  • Lee RWH, Huttner WB (1983) Tyrosine-O-sulfated proteins of PC12 pheochromocytoma cells and their sulfation by a tyrosylprotein sulfotransferase. J Biol Chem 258:11326–11334

    PubMed  CAS  Google Scholar 

  • Leube RE, Kaiser P, Seiter A, Zimbelmann R, Franke WW, Rehm H, Knaus P, Prior P, Betz H, Reinke H, Beyreuther K, Wiedenmann B (1987) Synyaptophysin: molecular organization and mRNA expression as determined from cloned cDNA. EMBO J 6:3261–3268

    PubMed  CAS  Google Scholar 

  • Leube RE, Wiedenmann B, Franke WW (1989) Topogenesis and specific vesicle sorting: synthesis of a neurodifferentiation-specific transmembrane protein from a gene transfected into non-neuroendocrine cells. Cell (in press)

  • Lloyd RV, Wilson BS (1983) Specific endocrine tissue marker defined by a monoclonal antibody. Science 222:628–630

    PubMed  CAS  Google Scholar 

  • Lloyd RV, Mervak T, Schmidt K, Warner TF, Wilson BS (1984) Immunohistochemical detection of chromogranin and neuron-specific enolase in pancreatic endocrine neoplasms. Am J Surg Pathol 8:607–614

    PubMed  CAS  Google Scholar 

  • Lloyd RV, Wilson BS, Kovacs K, Ryan N (1985a) Immunohistochemical localization of chromogranin in human hypophyses and pituitary adenomas. Arch Pathol Lab Med 109:515–517

    PubMed  CAS  Google Scholar 

  • Lloyd RV, Blaivas M, Wilson BS (1985b) Distribution of chromogranin and S100 protein in normal and abnormal adrenal medullary tissues. Arch Pathol Lab Med 109:633–635

    PubMed  CAS  Google Scholar 

  • Lloyd RV, Sisson JC, Shapiro B, Verhofstad AA (1986) Immunohistochemical localization of epinephrine, norepineph-119 rine, catecholamine-synthesizing enzymes, and chromogranin in neuroendocrine cells and tumors. Am J Pathol 125:45–54

    PubMed  CAS  Google Scholar 

  • Lloyd RV, Cano M, Rosa P, Hille A, Huttner WB (1988) Distribution of chromogranin A and secretogranin I (chromogranin B) in neuroendocrine cells and tumors. Am J Pathol 130:296–304

    PubMed  CAS  Google Scholar 

  • Lowe AW, Madeddu L, Kelly RB (1988) Endocrine secretory granules and neuronal synaptic vesicles have three integral membrane proteins in common. J Cell Biol 106:51–59

    PubMed  CAS  Google Scholar 

  • Lundberg JM, Hökfelt T (1983) Coexistence of peptides and classical neurotransmitters. Trends Neurosci 6:325–333

    CAS  Google Scholar 

  • Manivel C, Wick MR, Sibley RK (1986) Neuroendocrine differentiation in Mullerian neoplasms. An immunohistochemical study of a “pure” endometrial small-cell carcinoma and a mixed Mullerian tumor containing small-cell carcinoma. Am J Clin Pathol 86:438–443

    PubMed  CAS  Google Scholar 

  • Marcinkiewicz M, Benjannet S, Cantin M, Seidah NG, Chretien M (1986) CNS distribution of a novel pituitary protein ‘7B2’: localization in secretory and synaptic vesicles. Brain Res 380:349–356

    PubMed  CAS  Google Scholar 

  • Matthew WD, Tsavaler L, Reichardt LF (1981) Identification of a synaptic vesicle-specific membrane protein with a wide distribution in neuronal and neurosecretory tissue. J Cell Biol 91:257–269

    PubMed  CAS  Google Scholar 

  • McNutt MA, Bolen JW (1985) Adenomatous tumor of the middle ear. An ultrastructural and immunocytochemical study. Am J Clin Pathol 84:541–547

    PubMed  CAS  Google Scholar 

  • Metz J, Gerstheimer FP, Herbst M (1986) Distribution of synaptophysin immunoreactivity in guinea pig heart. Histochemistry 86:221–224

    PubMed  CAS  Google Scholar 

  • Miettinen M (1987) Synaptophysin and neurofilament proteins as markers for neuroendocrine tumors. Arch Pathol Lab Med 111:813–818

    PubMed  CAS  Google Scholar 

  • Miettinen M, Rapola J (1987) Synaptophysin — an immunohistochemical marker for childhood neuroblastoma. Acta Pathol Microbiol Immunol 95:167–170

    CAS  Google Scholar 

  • Miller RR, Sumner HW (1982) Argyrophilic cell hyperplasia and an atypical carcinoid tumor in chronic ulcerative colitis. Cancer 50:2920–2925

    PubMed  CAS  Google Scholar 

  • Miura K, Shirasawa H (1988) Primary carcinoid of the liver. Am J Clin Pathol 89:561–564

    PubMed  CAS  Google Scholar 

  • Mooi WJ, Dewar A, Springall D, Polak JM, Addis B (1988) Non-small cell lung carcinomas with neuroendocrine features. A light microscopic, immunohistochemical and ultrastructural study of 11 cases. Histopathology 13:329–337

    PubMed  CAS  Google Scholar 

  • Müller J, Kirchner T, Müller-Hermelink HK (1987) Gastric endocrine cell hyperplasia and carcinoid tumors in atrophic gastritis type A. Am J Sur Pathol 11:909–917

    Google Scholar 

  • Murphy MN, Glennon PG, Diocee MS, Wick MR, Cavers DJ (1986) Nonsecretory parathyroid carcinoma of the mediastinum. Light microscopic, immunocytochemical, and ultrastructural features of a case, and review of the literature. Cancer 58:2468–2476

    PubMed  CAS  Google Scholar 

  • Nash SV, Said JW (1986) Gastroenteropancreatic neuroendocrine tumors. A histochemical and immunohistochemical study of epithelial (keratin proteins, carcinoembryonic antigen) and neuroendocrine (neuron-specific enolase, bombesin and chromogranin) markers in foregut, midgut, and hindgut tumors. Am J Clin Pathol 86:415–422

    PubMed  CAS  Google Scholar 

  • Navone F, Greengard P, De Camilli P (1984) Synapsin I in nerve terminals: selective association with small synaptic vesicles. Science 226:1209–1211

    PubMed  CAS  Google Scholar 

  • Navone F, Jahn R, Di Gioia G, Stukenbrok H, Greengard P, De Camilli P (1986) Protein 38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells. J Cell Biol 103:2511–2527

    PubMed  CAS  Google Scholar 

  • Nesland JM, Holm R, Johannessen JV (1986) A study of different markers for neuroendocrine differentiation in breast carcinomas. Pathol Res Pract 181:524–530

    PubMed  CAS  Google Scholar 

  • Nolan JA, Trojanowski JQ, Hogue-Angeletti R (1985) Neurons and neuroendocrine cells contain chromogranin: detection of the molecule in normal bovine tissues by immunochemical and immunohistochemical methods. J Histochem Cytochem 33:791–798

    PubMed  CAS  Google Scholar 

  • O’Connor DT, Burton D, Deftos LJ (1983a) Chromogranin A: immunohistology reveals its universal occurrence in normal polypeptide hormone producing endocrine glands. Life Sci 33:1657–1663

    PubMed  CAS  Google Scholar 

  • O’Connor DT, Burton D, Deftos LJ (1983b) Immunoreactive human chromogranin A in diverse polypeptide hormone producing human tumors and normal endocrine tissues. J Clin Endocrinol Metab 57:1084–1086

    PubMed  CAS  Google Scholar 

  • O’Connor DT, Bernstein KN (1984) Radioimmunoassay of chromogranin A in plasma as a measure of exocytotic sympathoadrenal activity in normal subjects and patients with pheochromocytoma. N Engl J Med 311:764–770

    PubMed  CAS  Google Scholar 

  • O’Connor DT, Deftos LJ (1986) Secretion of chromogranin A by peptide-producing endocrine neoplasms. N Engl J Med 314:1145–1151

    PubMed  CAS  Google Scholar 

  • Obendorf D, Schwarzenbrunner U, Fischer-Colbrie R, Laslop A, Winkler H (1988) In adrenal medulla synaptophysin (protein p38) is present in chromaffin granules in a special vesicle population. J Neurochem 51:1573–1580

    PubMed  CAS  Google Scholar 

  • Oka T, Yoshioka T, Shrestha GR, Koide T, Sonoda T, Hosokawa S, Onoe K, Sakurai M (1988) Immunohistochemical study of nodular hyperplastic thyroid glands in patient with secondary hyperparathyroidism. Virchows Arch [A] 413:53–60

    CAS  Google Scholar 

  • Okuno S, Fujisawa H (1984) Purification and characterization of rat dopamine beta-monooxygenase and monoclonal antibodies to the enzyme. Biochem Biophys Acta 799:260–269

    PubMed  CAS  Google Scholar 

  • Ooi A, Mai M, Ogino T, Ueda H, Kitamura T, Takahashi Y, Kawahara, E, Nakanishi I (1988) Endocrine differentiation of gastric adenocarcinoma. The prevalence as evaluated by immunoreactive chromogranin A and its biological significance. Cancer 62:1096–1104

    PubMed  CAS  Google Scholar 

  • Orci L, Ravazzola M, Amherdt M, Perrelet A, Powell S, Quinn DL, Moore H-PH (1987) The trans-most cisternae of the Golgi complex: A compartment for sorting of secretory and plasma membrane proteins. Cell 51:1039–1051

    PubMed  CAS  Google Scholar 

  • Ortonne JP, Petchot-Bacque JP, Verrando P, Pisani A, Pautrat G, Bernard F (1988) Normal Merkel cells express a synaptophysin-like immunoreactivity. Dermatologica 177:1–10

    PubMed  CAS  Google Scholar 

  • Påhlman S, Esscher T, Nilsson K (1986) Expression of gammasubunit of enolase, neuronspecific enolase, in human nonneuroendocrine tumors and derived cell lines. Lab Invest 54:554–560

    PubMed  Google Scholar 

  • Pang DT, Wang JK, Valtorta F, Benfenati F, Greengard P (1988) Protein tyrosine phosphorylation in synaptic vesicles. Proc Natl Acad Sci USA 85:762–766

    PubMed  CAS  Google Scholar 

  • Pearse AGE (1974) The APUD cell concepts and its implications in pathology. Pathol Ann 9:27–41

    CAS  Google Scholar 

  • Pearse AGE, Takor Takor T (1979) Embryology of the diffuse neuroendocrine system and its relationship to common peptides. Fed Proc 38:2288–2294

    PubMed  CAS  Google Scholar 

  • Phillips JH, Pryde JG (1987) The chromaffin granule: A model system for the study of hormones and neurotransmitters. Ann NY Acad Sci 493:27–42

    PubMed  CAS  Google Scholar 

  • Piehl MR, Gould VE, Warren WH, Lee I, Radosevich JA, Ma Y, Rosen ST (1988) Immunohistochemical identification of exocrine and neuroendocrine subsets of large cell lung carcinomas. Pathol Res Pract 183:675–682

    PubMed  CAS  Google Scholar 

  • Pietroletti R, Bishop AE, Carlei F, Bonamico M, Lloyd RV, Wilson BS, Ceccamea A, Lezoche E, Speranzy V, Polak JM (1986) Gut endocrine cell population in coeliac disease estimated by immunocytochemistry using a monoclonal antibody to chromogranin. Gut 27:838–843

    PubMed  CAS  Google Scholar 

  • Pruss RM (1987) Monoclonal antibodies to chromaffin cells can distinguish proteins specific to or specifically excluded from chromaffin granules. Neuroscience 22:141–147

    PubMed  CAS  Google Scholar 

  • Pruss RM, Shepard EA (1987) Cytochrome b561 can be detected in many neuroendocrine tissues using a specific monoclonal antibody. Neuroscience 22:149–157

    PubMed  CAS  Google Scholar 

  • Rehm H, Wiedenmann B, Betz H (1986) Molecular characterization of synaptophysin, a major calcium-binding protein of the synaptic vesicle membrane. EMBO J 5:535–541

    PubMed  CAS  Google Scholar 

  • Reiffen FU, Gratzl M (1986) Ca2+ binding to chromaffin vesicle matrix proteins: effect of pH, Mg2+, and ionic strength. Biochemistry 25:4402–4406

    PubMed  CAS  Google Scholar 

  • Rindi G, Buffa R, Sessa F, Tortora O, Solcia E (1986) Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Distribution, distinction from costored hormones/prohormones and relationship with the argyrophil component of secretory granules. Histochemistry 85:19–28

    PubMed  CAS  Google Scholar 

  • Rode J, Dhillon AP, Papadaki L, Stockbrügger R, Thompson RJ, Moss E, Cotton PB (1986) Pernicious anaemia and mucosal endocrine cell proliferation of the non-antral stomach. Gut 27:789–798

    PubMed  CAS  Google Scholar 

  • Rosa P, Zanini A (1981) Characterization of adenohypophysial polypeptides by two-dimensional gel electrophoresis. Mol Cell Endocrinol 24:181–193

    PubMed  CAS  Google Scholar 

  • Rosa P, Fumagalli G, Zanini A, Huttner WB (1985a) The major tyrosine-sulfated protein of the bovine anterior pituitary is a secretory protein present in gonadotrophs, thyrotrophs, mammotrophs and corticotrophs. J Cell Biol 100:928–937

    PubMed  CAS  Google Scholar 

  • Rosa P, Hille A, Lee RW, Zanini A, De Camilli P, Huttner WB (1985b) Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway. J Cell Biol 101:1999–2011

    PubMed  CAS  Google Scholar 

  • Rundle S, Somogyi P, Fischer-Colbrie R, Hagn C, Winkler H, Chubb IW (1986) Chromogranin A, B and C: immunohistochemical localization in ovine pituitary and the relationship with hormone-containing cells. Regulat Pept 16:217–233

    CAS  Google Scholar 

  • Said JW, Vimadalal S, Nash G, Shintaku IP, Heusser RC, Sassoon AF, Lloyd RV (1985) Immunoreactive neuron-specific enolase, bombesin, and chromogranin as markers for neuroendocrine lung tumors. Hum Pathol 16:236–240

    PubMed  CAS  Google Scholar 

  • Scheithauer BW, Nora FE, Lechago J, Wick MR, Crawford BG, Weiland LH, Carney JA (1986) Duodenal gangliocytic paraganglioma: A Clinico-pathologic and immunocytochemical study of 11 cases. Am J Clin Pathol 86:559–565

    PubMed  CAS  Google Scholar 

  • Schilling K, Gratzl M (1988) Quantification of p38/synaptophysin in highly purified adrenal medullary chromaffin vesicles. FEBS Lett 233:22–24

    PubMed  CAS  Google Scholar 

  • Schmechel D, Marangos PJ, Brightman M (1978) Neuron-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature 276:834–836

    PubMed  CAS  Google Scholar 

  • Schmid KW, Fischer-Colbrie R, Hagn C, Jasani B, Williams ED, Winkler H (1987) Chromogranin A and B and secretogranin II in medullary carcinomas of the thyroid. Am J Surg Pathol 11:551–556

    PubMed  CAS  Google Scholar 

  • Schmidt WE, Siegel EG, Lamberts R, Gallwitz B, Creutzfeldt W (1988a) Pancreastatin: molecular and immunocytochemical characterization of a novel peptide in porcine and human tissues. Endocrinology 123:1395–1404

    PubMed  CAS  Google Scholar 

  • Schmidt WE, Siegel EG, Kratzin H, Creutzfeldt W (1988b) Isolation and primary structure of tumor-derived peptides related to human pancreastatin and chromogranin A. Proc Natl Acad Sci USA 85:8231–8235

    PubMed  CAS  Google Scholar 

  • Schober M, Fischer-Colbrie R, Schmid KW, Bussolati G, O’Connor DT, Winkler H (1987) Comparison of chromogranins A, B and secretogranin II in human adrenal medulla and pheochromocytoma. Lab Invest 57:385–391

    PubMed  CAS  Google Scholar 

  • Schroeder S, Boecker W, Baisch H, Burk CG, Arps H, Meiners I, Kastendieck H, Heitz PU, Kloeppel G (1988) Prognosic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content. Cancer 61:806–816

    Google Scholar 

  • Schuldiner S, Gabizon R, Stern Y, Suchi R (1987) The amine transporter from bovine chromaffin granules: Photolabeling and partial purification. Ann NY Acad Sci 493:189–193

    PubMed  CAS  Google Scholar 

  • Schwechheimer K, Wiedenmann B, Franke WW (1987) Synaptophysin: a reliable marker for medulloblastomas. Virchows Arch [A] 411:53–59

    CAS  Google Scholar 

  • Seidah NG, Hendy GN, Hamelin J, Paquin J, Lazure C, Metters KM, Rossier J, Chrétien M (1987) Chromogranin A can act as a reversible processing enzyme inhibitor. FEBS 211:144–150

    CAS  Google Scholar 

  • Sekiya K, Ghatei MA, Minamino N, Bretherton-Watt D, Matsuo H, Bloom SR (1988) Isolation of human pancreastatin fragment containing the active sequence from a glucagonoma. FEBS Lett 228:153–156

    PubMed  CAS  Google Scholar 

  • Siegel RE, Iacangelo A, Park J, Eiden LE (1988) Chromogranin A biosynthetic cell populations in bovine endocrine and neuronal tissues: detection by in situ hybridization histochemistry. Mol Endocrinol 2:368–674

    PubMed  CAS  Google Scholar 

  • Sietzen M, Schober M, Fischer-Colbrie R, Scherman D, Sperk G, Winkler H (1987) Rat adrenal medulla: levels of chromogranins, enkephalins, dopamine beta-hydroxylase and of the amine transporter are changed by nervous activity and hypophysectomy. Neuroscience 22:131–139

    PubMed  CAS  Google Scholar 

  • Sikri KL, Varndell IM, Hamid QA, Wilson BS, Kameya T, Ponder BA, Lloyd RV, Bloom SR, Polak JM (1985) Medullary carcinoma of the thyroid. An immunocytochemical and histochemical study of 25 cases using eight separate markers. Cancer 56:2481–2491

    PubMed  CAS  Google Scholar 

  • Silver MM, Hearn SA, Lines LD, Troster M (1988) Calcitonin and chromogranin A localization in medullary carcinoma of the thyroid by immunoelectron microscopy. J Histochem Cytochem 36:1031–1036

    PubMed  CAS  Google Scholar 

  • Simon J-P, Bader M-F, Aunis D (1988) Secretion from chromaffin cells is controlled by chromogranin A-derived peptides. Proc Natl Acad Sci USA 85:1712–1716

    PubMed  CAS  Google Scholar 

  • Smith AD, Winkler H (1967) Purification and properties of an acidic protein from chromaffin granules of bovine adrenal medulla. Biochem J 103:483–492

    PubMed  CAS  Google Scholar 

  • Somogyi P, Hodgson AJ, DePotter RW, Fischer-Colbrie R, Schober M, Winkler H, Chubb IW (1984) Chromogranin immunoreactivity in the central nervous system. Brain Res 320:193–230

    PubMed  CAS  Google Scholar 

  • Stagno PA, Petras RE, Hart WR (1987) Strumal carcinoids of the ovary. Arch Pathol Lab Med 111:440–446

    PubMed  CAS  Google Scholar 

  • Stefaneanu L, Ryan N, Kovacs K (1988) Immunocytochemical localization of synaptophysin in human hypophyses and pituitary adenomas. Arch Pathol Lab Med 112:801–804

    PubMed  CAS  Google Scholar 

  • Stewart LC, Klinman JP (1988) Dopamine beta-hydroxylase of adrenal chromaffin granules: structures and function. Ann Rev Biochem 57:551–592

    PubMed  CAS  Google Scholar 

  • Südhof TC, Lottspeich F, Greengard P, Mehl E, Jahn R (1987) A synaptic vesicle protein with a novel cytoplasmic domain and four transmembrane regions. Science 238:1142–1144

    PubMed  Google Scholar 

  • Tatemoto K, Efendic S, Mutt V, Makk G, Feistner GJ (1986) Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 324:476–478

    PubMed  CAS  Google Scholar 

  • Thomas L, Hartung K, Langosch D, Rehm H, Bamberg E, Franke WW, Betz H (1988) Identification of synaptophysin as a hexameric channel protein of the synaptic vesicle membrane. Science 242:1050–1053

    PubMed  CAS  Google Scholar 

  • Tixier-Vidal A, Faivre-Bauman A, Picart R, Wiedenmann B (1988) Immunoelectron microscopic localization of synaptophysin in a Golgi subcompartment of developing hypothalamic neurons. Neuroscience 26:847–861

    PubMed  CAS  Google Scholar 

  • Tooze J, Tooze SA, Fuller SD (1987) Sorting of progeny coronavirus from condensed secretory proteins at the exit from the trans-Golgi network of AtT20 cells. J Cell Biol 105:1215–1226

    PubMed  CAS  Google Scholar 

  • Tougard C, Nasciutti L-E, Picart R, Tixier-Vidal A, Huttner WB (1989) Subcellular distribution of secretogranins I and II in GH3 rat tumoral prolactin (PRL) cells as revealed by electron microscopic immunocytochemistry. J Histochem Cytochem (in press)

  • Turbat-Herrera EA, Herrera GA, Gore I, Lott RL, Grizzle WE, Bonnin JM (1988) Neuroendocrine differentiation in prostatic carcinomas. Arch Pathol Lab Med 112:1100–1105

    PubMed  CAS  Google Scholar 

  • Ulich TR, Kollin M, Lewin KJ (1988) Composite gastric carcinoma: report of a tumor of the carcinoma-carcinoid spectrum. Arch Pathol Lab Med 112:91–93

    PubMed  CAS  Google Scholar 

  • Ulich TR, Liao SY, Layfield L, Romansky S, Cheng L, Lewin KJ (1986) Endocrine and tumor differentiation markers in poorly differentiated small-cell carcinoids of the cervix and vagina. Arch Pathol Lab Med 110:1054–1057

    PubMed  CAS  Google Scholar 

  • Varndell IM, Lloyd RV, Wilson BS, Polak JM (1985) Ultrastructural localization of chromogranin: a potential marker for the electron microscopical recognition of endocrine cell secretory granules. Histochem J 17:981–992

    PubMed  CAS  Google Scholar 

  • Volknandt W, Schober M, Fischer-Colbrie R, Zimmermann H, Winkler H (1987) Cholinergic nerve terminals in the rat diaphragm are chromogranin A immunoreactive. Neurosci Lett 81:241–244

    PubMed  CAS  Google Scholar 

  • Walts AE, Said JW, Shintaki IP, Lloyd RV (1985) Chromogranin as a marker of neuroendocrine cells in cytologic material — an immunocytochemical study. Am J Clin Pathol 84:273–277

    PubMed  CAS  Google Scholar 

  • Weiler R, Feichtinger H, Schmid KW, Fischer-Colbrie R, Grimelius L, Cedermark B, Papotti M, Bussolati G, Winkler H (1987) Chromogranin A and B and secretogranin II in bronchial and intestinal carcinoids. Virchows Arch [A] 412:103–109

    CAS  Google Scholar 

  • Weiler R, Fischer-Colbrie R, Schmid KW, Feichtinger H, Bussolati G, Grimelius L, Krisch K, Kerl H, O’Connor D, Winkler H (1988) Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors. Am J Surg Pathol 12:877–884

    PubMed  CAS  Google Scholar 

  • Wick MR, Weatherby RP, Weiland LH (1987) Small cell neuroendocrine carcinoma of the colon and rectum: Clinical, histologic and ultrastructural study and immunohistochemical comparison with cloacogenic carcinoma. Hum Pathol 18:9–21

    PubMed  CAS  Google Scholar 

  • Wick MR, Stanley SJ, Swanson PE (1988) Immunohistochemical diagnosis of sinonasal melanoma, carcinoma, and neuroblastoma with monoclonal antibodies HMB-45 and antisynaptophysin. Arch Pathol Lab Med 112:616–620

    PubMed  CAS  Google Scholar 

  • Wiedenmann B, Franke WW (1985) Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38000 characteristic of presynaptic vesicles. Cell 41:1017–1028

    PubMed  CAS  Google Scholar 

  • Wiedenmann B, Franke WW, Kuhn C, Moll R, Gould VE (1986) Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci USA 83:3500–3504

    PubMed  CAS  Google Scholar 

  • Wiedenmann B, Kuhn C, Schwechheimer K, Waldherr R, Raue F, Brandeis WE, Kommerell B, Franke WW (1987a) Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting. Am J Clin Pathol 88:560–569

    PubMed  CAS  Google Scholar 

  • Wiedenmann B, Rehm H, Franke WW (1987b) Synapotphysin, an integral membrane protein of vesicles present in normal and neoplastic neuroendocrine cells. Ann NY Acad Sci 493:500–503

    CAS  Google Scholar 

  • Wiedenmann B, Waldherr R, Rosa R, Huttner W (1987c) Nachweis und Identifikation von Sekretogranin I im Gewebe und Serum von Patienten von neuroendokrinen Tumoren. Z Gastroenterologie 8, XXV: 589

    Google Scholar 

  • Wiedenmann B, Waldherr R, Buhr H, Hille A, Rosa P, Huttner WB (1988a) Identification of gastroenteropancreatic neuroendocrine cells in normal and neoplastic human tissue with antibodies against synaptophysin, chromogranin A, secretogranin I (chromogranin B), and secretogranin II. Gastroenterology 95:1364–1374

    PubMed  CAS  Google Scholar 

  • Wiedenmann B, Rehm H, Knierim M, Becker C-M (1988b) Fractionation of synaptophysin-containing vesicles from rat brain and cultured PC12 pheochromocytoma cells. FEBS Lett 240:71–77

    PubMed  CAS  Google Scholar 

  • Wilson BS, Lloyd RV (1984) Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol 115:458–468

    PubMed  CAS  Google Scholar 

  • Winkler H, Westhead E (1980) The molecular organization of the chromaffin granule. Neuroscience 5:1803–1823

    PubMed  CAS  Google Scholar 

  • Winkler H, Apps DK, Fischer-Colbrie R (1986) The molecular function of adrenal chromaffin granules: established facts and unresolved topics. Neuroscience 18:261–290

    PubMed  CAS  Google Scholar 

  • Wohlfarter T, Fischer-Colbrie R, Hogue-Angeletti R, Eiden LE, Winkler H (1988) Processing of chromogranin A within chromaffin granules starts at Cand N-terminal cleavage sites. FEBS Lett 231:67–70

    PubMed  CAS  Google Scholar 

  • Yoshie S, Hagn C, Ehrhart M, Fischer-Colbrie R, Grube D, Winkler H, Gratzl M (1987) Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet. Histochemistry 87:99–106

    PubMed  CAS  Google Scholar 

  • Zanini A, Rosa P (1981) Characterization of adenohypophyseal polypeptides by two-dimensional gel electrophoresis. Mol Cell Endocrinol 24:165–179

    PubMed  CAS  Google Scholar 

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  1. Department of Internal Medicine, University of Heidelberg Medical School, Bergheimer Strasse 58, D-6900, Heidelberg, Federal Republic of Germany

    Bertram Wiedenmann

  2. Cell Biology Programme European Molecular Biology Laboratory, Postfach 102209, D-6900, Heidelberg, Federal Republic of Germany

    Wieland B. Huttner

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Wiedenmann, B., Huttner, W.B. Synaptophysin and chromogranins/secretogranins widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. Virchows Archiv B Cell Pathol 58, 95–121 (1989). https://doi.org/10.1007/BF02890062

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Keywords

  • Adrenal Medulla
  • Islet Cell Tumor
  • Chromaffin Granule
  • Bovine Anterior Pituitary
  • Chromaffin Granule Membrane