Abstract
Most neuroendocrine tumors produce and secrete a multitude of peptide hormones and amines. Some of these substances cause a specific clinical syndrome: carcinoid, Zollinger-Ellison, hyperglycemic, glucagonoma and WDHA syndrome. Specific markers for these syndromes are basal and/or stimulated levels of urinary 5-HIAA, serum or plasma gastrin, insulin, glucagon and vasoactive intestinal polypeptide, respectively. Some carcinoid tumors and about one third of endocrine pancreatic tumors do not present any clinical symptoms and are called ‘nonfunctioning’ tumors. Therefore, general tumor markers such as chromogranin A, pancreatic polypeptide, serum neuron-specific enolase and subunits of glycoprotein hormones have been used for screening purposes in patients without distinct clinical hormone-related symptoms. Among these general tumor markers chromogranin A, although its precise function is not yet established, has been shown to be a very sensitive and specific serum marker for various types of neuroendocrine tumors. This is because it may also be elevated in many cases of less well-differentiated tumors of neuroendocrine origin that do not secrete known hormones. At the moment, chromogranin A is considered the best general neuroendocrine serum or plasma marker available both for diagnosis and therapeutic evaluation and is increased in 50–100% of patients with various neuroendocrine tumors. Chromogranin A serum or plasma levels reflect tumor load, and it may be an independent marker of prognosis in patients with midgut carcinoids.
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References
1.
Norheim I, Öberg K, Theodorsson-Norheim E, Lindgren PG, Lundqvist G, Magnusson A, Wide L, Wilander E: Malignant carcinoid tumors: An analysis of 103 patients with regard to tumor localization, hormone production and survival. Ann Surg 1987;206:115–125.
[PubMed]
2.
Eriksson B, Arnberg H, Lindgren PG, Lörelius LE, Magnusson A, Lundqvist G, Skogseid B, Wide L, Wilander E, Öberg K: Neuroendocrine pancreatic tumours: Clinical presentation, biochemical and histopathological findings in 84 patients. J Intern Med 1990;228:103–113.
[PubMed]
3.
Janson ET, Holmberg L, Stridsberg M, Eriksson B, Theodorsson E, Wilander E, Öberg K: Carcinoid tumors. Analysis of prognostic factors and survival in 301 patients from a referral center. Ann Oncol 1997;8:685–690.
[PubMed]
4.
Norheim I, Theodorsson-Norheim E, Brodin E, Öberg K: Tachykinins in carcinoid tumors. Their use as a tumor marker and possible role in the carcinoid flush. J Clin Endocrinol Metab 1986;63:605–612.
[PubMed]
5.
McGuigan JE, Wolfe MM: Secretin injection test in the diagnosis of gastrinoma. Gastroenterology 1980;79:1324–1327.
[PubMed]
6.
Wiedemann B, Huttner WB: Synaptophysin and chromogranins/secretogranins – Widespread constituents of distinct type of neuroendocrine vesicles and new tools in tumour diagnosis. Virchows Arch B Cell Pathol Incl Mol Pathol 1989;58:95–121.
[PubMed]
7.
Winkler H, Fischer-Colbrie B: The chromogranins A and B, the first 25 years and future perspectives. Neuroscience 1992;49:497–528.
[PubMed]
8.
Iacangelo AL, Eiden LE: Chromogranin A: Current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway. Regul Pept 1995;58:65–88.
[PubMed]
9.
Eiden LE, Huttner WB, Mallet J, O’Connor DT, Winkler H, Zanini AA: A nomenclature proposal for the chromogranin/secretogranin proteins. Neuroscience 1987;21:1019–1021.
[PubMed]
10.
Blaschko H, Comline RS, Schneider FH, Silver M, Smith AD: Secretion of a chromaffin granule protein, chromogranin from the adrenal gland after splanchnic stimulation. Nature 1967;215:58–59.
[PubMed]
11.
Deftos LJ: Chromogranin A, its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev 1991;12:181–187.
[PubMed]
12.
O’Connor DT, Burton D, Deftos LJ: Immunoreactive chromogranin A in diverse polypeptide hormone producing tumors and normal endocrine tissues. J Clin Endocrinol Metab 1983;57:1084–1086.
[PubMed]
13.
Stridsberg M, Öberg K, Li Q, Engström U, Lundqvist G: Measurements of chromogranin A, chromogranin B (secretogranin I), chromogranin C (secretogranin II) and pancreastatin in plasma and urine from patients with carcinoid tumours and endocrine pancreatic tumours. J Endocrinol 1995;144:49–59.
[PubMed]
14.
Eriksson B, Arnberg H, Öberg K, Hellman U, Lundqvist G, Wernstedt C, Wilander E: A polyclonal antiserum against chromogranin A and B – A new sensitive marker for neuroendocrine tumours. Acta Endocrinol (Copenh) 1990;122:145–155.
[PubMed]
15.
Wu HJ, Rozansky DJ, Parmer RJ, Gill BM, O’Connor DT: Structure and function of the chromogranin A gene. Clues to evolution and tissue specific expression. J Biol Chem 1991;266:13130–13134.
[PubMed]
16.
Helman LJ, Ahn TG, Levine MA, Allison A, Cohen PS, Cooper MJ, Cohn DV, Israel MA: Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA. J Biol Chem 1988;263:11559–11563.
[PubMed]
17.
Benedum UM, Lamouroux A, Konecki DS, et al: 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 1987;6:1203–1211.
[PubMed]
18.
Chanat E, Weiss U, Huttner WB, Tooze SA: Reduction of the disulfide bond of chromogranin B (secretogranin I) in the trans-Golgi network causes its missorting to the constitutive secretory pathway. EMBO J 1993;12:2159–2168.
[PubMed]
19.
Iacangelo A, Fischer-Colbrie R, Koller KJ, Brownstein MJ, Eiden LE: The sequence of porcine chromogranin can serve as the precursor for the biologically active hormone pancreastatin. Endocrinology 1988;122:2339–2341.
[PubMed]
20.
Tatemoto K, Efendic S, Mutt V, Makk HL, Feistner GJ: Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 1986;324:476–478.
[PubMed]
21.
Ishizuka J, Asada I, Poston GJ, Lluis F, Tatemoto K, Greeby GH Jr, Thompson JC: Effect of pancreastatin on pancreatic endocrine and exocrine secretion. Pancreas 1989;4:277–281.
[PubMed]
22.
Fasciotto BH, Trauss CA, Greeley GH, Cohn DV: Parastatin (porcine chromogranin A347-419), a novel chromogranin A-derived peptide, inhibits parathyroid cell secretion. Endocrinology 1993;135:337–342.
23.
Lewis JJ, Goldering JR, Asher VA, Modlin IM: Pancreastatin: A novel peptide inhibitor of parietal cell signal transduction. Biochem Biophys Res Commun 1989;163:667–673.
[PubMed]
24.
Schmidt WE, Siegel EG, Lamberts R, Gallwitz B, Creutzfeldt W: Pancreastatin: Molecular and immunocytochemical characterization of a novel peptide in porcine and human tissues. Endocrinology 1988;123:1395–1404.
[PubMed]
25.
Hutton JC, Hansen F, Peshavaria M: Proteolytic processing of chromogranin A in purified insulin granules. Formation of a 20 kDa N-terminal fragment (betagranin) by the concerted action of a Ca2+-dependent endopeptidase and carboxypeptidase. Biochemistry 1987;244:457–464.
26.
Drees BM, Hamilton JW: Processing of chromogranin A by bovine parathyroid secretory granules: Production and secretion of N-terminal fragments. Endocrinology 1994;134:2057–2063.
[PubMed]
27.
Aardal S, Helle KB: The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its dependence of extracellular calcium in isolated segments of human blood vessels. Regul Pept 1992;41:9–18.
[PubMed]
28.
Russell J, Gee P, Liu SM, Angeletti RH: Inhibition of parathyroid hormone secretion by amino-terminal chromogranin peptides. Endocrinology 1994;135:337–342.
[PubMed]
29.
Gasparri A, Sidoli A, Perez-Sanchez L, Longhi R, Siccardi AG, Marchisio PC, Corti A: Chromogranin A fragments modulate cell adhesion. J Biol Chem 1997;272:20835–20843.
[PubMed]
30.
Fasciotto BH, Gorr SU, De Franco DJ, Levine MA, Cohn DV: Pancreastatin, a presumed product of chromogranin-A (secretory protein-I) processing, inhibits secretion from porcine parathyroid cells in culture. Endocrinology 1989;125:1617–1622.
[PubMed]
31.
Galindo E, Rill A, Bader MF, Aunis D: Chromostatin, a 20-amino acid chromogranin chromogranin cell secretion. Proc Natl Acad Sci USA 1991;88:1426–1430.
[PubMed]
32.
Galindo E, Mendez M, Calvo S, Gonzalez-Garcia C, Cena V, Hubert P, Bader MF, Annis D: Chromostatin receptors control calcium channel activity in adrenal chromaffin cells. J Biol Chem 1992;267:407–412.
[PubMed]
33.
Deftos LJ, Gazdar AF, Hogue-Angeletti R, Mullen PS, Burton DW: Distinct patterns of chromogranin A-related species can be demonstrated in endocrine cells. Bone Miner 1990;9:169–178.
[PubMed]
34.
Larsson L, Alumets J, Eriksson B, Håkansson R, Lundqvist G, Öberg K, Sundler F: Antiserum directed against chromogranin A and B (CAB) is a useful marker for peptide hormone-producing endocrine cells and tumours. Endocrine Pathol 1992;3:14–22.
35.
Borch K, Stridsberg M, Burman P, Rehfeld JF: Basal chromogranin-A and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-A gastritis. Scand J Gastroenterol 1997;32:198–202.
[PubMed]
36.
Eriksson B, Öberg K: Peptide hormones as tumor markers in neuroendocrine gastrointestinal tumors. Acta Oncol 1991;30:477–483.
[PubMed]
37.
Granberg D, Stridsberg M, Seensalu R, Eriksson B, Lundqvist G, Öberg K, Skogseid B: Plasma chromogranin A in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metabol 1999;84:2712–2717.
[PubMed]
38.
Bajetta E, Ferrari L, Merlonetti A, Celio L, Procopio G, Artale S, Zilembo N, Di Bartholomeo M, Serregni E, Bombardieri E: Chromogranin A, neuron-specific enolase, carcinoembryonic antigen and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors. Cancer 1999;86:858–865.
[PubMed]
39.
Kadmon D, Thompson TC, Lynch GR, Scardino PT: Elevated plasma chromogranin-A concentrations in prostatic carcinoma. J Urol 1991;146:358–361.
[PubMed]
40.
Deftos LJ, Nakada S, Burton DW, Di Sant’Agnese PA, Cockett AT, Abrahamsson PA: Immunoassay and immunohistology studies of chromogranin A as a neuroendocrine marker in patients with carcinoma of the prostate. Urology 1996;48:58–62.
[PubMed]
41.
Sundaresan V, Reeve JG, Stenning S, Stewart S, Bleehen NM: Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumors. Br J Cancer 1991;64:333–338.
[PubMed]
42.
Cryer PE, Wortsman J, Shah SD, Nowak RM, Deftos LJ: Plasma chromogranin A as marker of sympaticochromaffin activity in humans. 1991;260:E243–E246.
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