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. 1989 Jun;83(6):1834–1842. doi: 10.1172/JCI114089

Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value.

K Sekiya 1, M A Ghatei 1, M J Salahuddin 1, A E Bishop 1, Q A Hamid 1, H Ibayashi 1, J M Polak 1, S R Bloom 1
PMCID: PMC303903  PMID: 2723061

Abstract

GAWK (chromogranin-B 420-493) is a 74 amino acid peptide recently isolated from human pituitaries. Using two different antibodies (directed against GAWK [1-17] and [20-38] fragments) GAWK-LI was measured in tumors from 194 patients and in the plasma of 434 patients by RIA. The highest tissue concentrations of GAWK-LI were found in pheochromocytoma (GAWK [1-17]-LI, 18,173 +/- 3,915; GAWK [20-38]-LI, 17,852 +/- 2,763 [mean +/- SEM] pmol/g wet wt tissue; n = 9), which were at least ten times higher than any other tumors producing GAWK-LI. High concentrations of GAWK-LI were also found in other types of endocrine tumors including carcinoid, medullary carcinoma of thyroid, pancreatic, and ACTH-producing lung tumors. On the other hand, low concentrations of GAWK-LI were found in nonendocrine tumors. Plasma concentrations of GAWK-LI were found to be elevated in patients with endocrine tumor, but more so in those with pancreatic tumors than with pheochromocytomas. Plasma concentrations returned to normal after successful tumor removal. Chromatographic profiles of GAWK-LI in extracts of pheochromocytomas and normal adrenals showed high molecular weight peaks that were absent in the extracts of other endocrine tumors and normal pancreas, suggesting differential tissue-specific processing. Thus GAWK-LI is produced by a variety of endocrine tumors and may serve as a plasma tumor marker, especially in patients with pancreatic endocrine tumors.

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Selected References

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  1. Angeletti R. H. Chromogranins and neuroendocrine secretion. Lab Invest. 1986 Oct;55(4):387–390. [PubMed] [Google Scholar]
  2. Avrameas S., Ternynck T. The cross-linking of proteins with glutaraldehyde and its use for the preparation of immunoadsorbents. Immunochemistry. 1969 Jan;6(1):53–66. doi: 10.1016/0019-2791(69)90178-5. [DOI] [PubMed] [Google Scholar]
  3. Benjannet S., Leduc R., Adrouche N., Falgueyret J. P., Marcinkiewicz M., Seidah N. G., Mbikay M., Lazure C., Chretien M. Chromogranin B (secretogranin I), a putative precursor of two novel pituitary peptides through processing at paired basic residues. FEBS Lett. 1987 Nov 16;224(1):142–148. doi: 10.1016/0014-5793(87)80438-6. [DOI] [PubMed] [Google Scholar]
  4. Benjannet S., Leduc R., Lazure C., Seidah N. G., Marcinkiewicz M., Chrétien M. GAWK, a novel human pituitary polypeptide: isolation, immunocytochemical localization and complete amino acid sequence. Biochem Biophys Res Commun. 1985 Jan 16;126(1):602–609. doi: 10.1016/0006-291x(85)90648-5. [DOI] [PubMed] [Google Scholar]
  5. Cohn D. V., Elting J. J., Frick M., Elde R. 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. 1984 Jun;114(6):1963–1974. doi: 10.1210/endo-114-6-1963. [DOI] [PubMed] [Google Scholar]
  6. Facer P., Bishop A. E., Lloyd R. V., Wilson B. S., Hennessy R. J., Polak J. M. Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract. Gastroenterology. 1985 Dec;89(6):1366–1373. doi: 10.1016/0016-5085(85)90657-2. [DOI] [PubMed] [Google Scholar]
  7. Fischer-Colbrie R., Frischenschlager I. Immunological characterization of secretory proteins of chromaffin granules: chromogranins A, chromogranins B, and enkephalin-containing peptides. J Neurochem. 1985 Jun;44(6):1854–1861. doi: 10.1111/j.1471-4159.1985.tb07179.x. [DOI] [PubMed] [Google Scholar]
  8. Fischer-Colbrie R., Lassmann H., Hagn C., Winkler H. Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissues. Neuroscience. 1985 Nov;16(3):547–555. doi: 10.1016/0306-4522(85)90191-5. [DOI] [PubMed] [Google Scholar]
  9. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  10. Huang W. M., Gibson S. J., Facer P., Gu J., Polak J. M. Improved section adhesion for immunocytochemistry using high molecular weight polymers of L-lysine as a slide coating. Histochemistry. 1983;77(2):275–279. doi: 10.1007/BF00506570. [DOI] [PubMed] [Google Scholar]
  11. Konecki D. S., Benedum U. M., Gerdes H. H., Huttner W. B. The primary structure of human chromogranin A and pancreastatin. J Biol Chem. 1987 Dec 15;262(35):17026–17030. [PubMed] [Google Scholar]
  12. Lloyd R. V., Blaivas M., Wilson B. S. Distribution of chromogranin and S100 protein in normal and abnormal adrenal medullary tissues. Arch Pathol Lab Med. 1985 Jul;109(7):633–635. [PubMed] [Google Scholar]
  13. Lloyd R. V., Cano M., Rosa P., Hille A., Huttner W. B. Distribution of chromogranin A and secretogranin I (chromogranin B) in neuroendocrine cells and tumors. Am J Pathol. 1988 Feb;130(2):296–304. [PMC free article] [PubMed] [Google Scholar]
  14. Lloyd R. V., Wilson B. S., Kovacs K., Ryan N. Immunohistochemical localization of chromogranin in human hypophyses and pituitary adenomas. Arch Pathol Lab Med. 1985 Jun;109(6):515–517. [PubMed] [Google Scholar]
  15. O'Connor D. T., Bernstein K. N. Radioimmunoassay of chromogranin A in plasma as a measure of exocytotic sympathoadrenal activity in normal subjects and patients with pheochromocytoma. N Engl J Med. 1984 Sep 20;311(12):764–770. doi: 10.1056/NEJM198409203111204. [DOI] [PubMed] [Google Scholar]
  16. O'Connor D. T., Burton D., Deftos L. J. Chromogranin A: immunohistology reveals its universal occurrence in normal polypeptide hormone producing endocrine glands. Life Sci. 1983 Oct 24;33(17):1657–1663. doi: 10.1016/0024-3205(83)90721-x. [DOI] [PubMed] [Google Scholar]
  17. O'Connor D. T., Burton D., Deftos L. J. Immunoreactive human chromogranin A in diverse polypeptide hormone producing human tumors and normal endocrine tissues. J Clin Endocrinol Metab. 1983 Nov;57(5):1084–1086. doi: 10.1210/jcem-57-5-1084. [DOI] [PubMed] [Google Scholar]
  18. O'Connor D. T. Chromogranin: widespread immunoreactivity in polypeptide hormone producing tissues and in serum. Regul Pept. 1983 Jul;6(3):263–280. doi: 10.1016/0167-0115(83)90145-3. [DOI] [PubMed] [Google Scholar]
  19. O'Connor D. T., Deftos L. J. Secretion of chromogranin A by peptide-producing endocrine neoplasms. N Engl J Med. 1986 May 1;314(18):1145–1151. doi: 10.1056/NEJM198605013141803. [DOI] [PubMed] [Google Scholar]
  20. O'Connor D. T., Frigon R. P. Chromogranin A, the major catecholamine storage vesicle soluble protein. Multiple size forms, subcellular storage, and regional distribution in chromaffin and nervous tissue elucidated by radioimmunoassay. J Biol Chem. 1984 Mar 10;259(5):3237–3247. [PubMed] [Google Scholar]
  21. O'Connor D. T., Frigon R. P., Sokoloff R. L. Human chromogranin A. Purification and characterization from catecholamine storage vesicles of human pheochromocytoma. Hypertension. 1984 Jan-Feb;6(1):2–12. doi: 10.1161/01.hyp.6.1.2. [DOI] [PubMed] [Google Scholar]
  22. Rindi G., Buffa R., Sessa F., Tortora O., Solcia E. 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. 1986;85(1):19–28. doi: 10.1007/BF00508649. [DOI] [PubMed] [Google Scholar]
  23. Sekiya K., Ghatei M. A., Minamino N., Bretherton-Watt D., Matsuo H., Bloom S. R. Isolation of human pancreastatin fragment containing the active sequence from a glucagonoma. FEBS Lett. 1988 Feb 8;228(1):153–156. doi: 10.1016/0014-5793(88)80606-9. [DOI] [PubMed] [Google Scholar]
  24. Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
  25. Suzuki H., Ghatei M. A., Williams S. J., Uttenthal L. O., Facer P., Bishop A. E., Polak J. M., Bloom S. R. Production of pituitary protein 7B2 immunoreactivity by endocrine tumors and its possible diagnostic value. J Clin Endocrinol Metab. 1986 Sep;63(3):758–765. doi: 10.1210/jcem-63-3-758. [DOI] [PubMed] [Google Scholar]
  26. Walts A. E., Said J. W., Shintaku I. P., Lloyd R. V. Chromogranin as a marker of neuroendocrine cells in cytologic material--an immunocytochemical study. Am J Clin Pathol. 1985 Sep;84(3):273–277. doi: 10.1093/ajcp/84.3.273. [DOI] [PubMed] [Google Scholar]
  27. Wilson B. S., Lloyd R. V. Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol. 1984 Jun;115(3):458–468. [PMC free article] [PubMed] [Google Scholar]
  28. Wynick D., Williams S. J., Bloom S. R. Symptomatic secondary hormone syndromes in patients with established malignant pancreatic endocrine tumors. N Engl J Med. 1988 Sep 8;319(10):605–607. doi: 10.1056/NEJM198809083191003. [DOI] [PubMed] [Google Scholar]

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