Summary
Carcinoid tumours (bronchial and intestinal) were analyzed by immunoblotting for the presence of chromogranin A, B and secretogranin II. In all tumours an antigen corresponding in electrophoretic behaviour to adrenal chromogranin A was present. Lung carcinoids (3 out of 5) contained a relatively high concentration of a proteoglycan form of this antigen in addition. Chromogranin B was found in all tumours. In one and two dimensional immunoblotting it appeared identical to the corresponding adrenal antigen. Secretogranin II was also present, however concentrations (especially in intestinal carcinoids) were low and variable. Furthermore, in intestinal tumours it differed from the adrenal antigen by having a slightly higher molecular size and a more alkaline pI. Immunohistochemistry revealed that the tumour tissues stained positively for all three antigens. For secretogranin II the staining in intestinal tumours was relatively weak and quite variable. These results should provide a defined basis for immunohistochemical screening of carcinoids for the chromogranin/secretogranin antigens.
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Arrigoni MG, Woolner LB, Bernatz PE (1972) Atypical carcinoid tumour of the lung. J Thorac Cardiovasc Surg 64:413–421
Burnette WN (1981) “Western blotting”: electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 112:195–203
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
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 Nat Acad Sci USA 79:6056–6059
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
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
Facer P, Bishop AE, Lloyd RV, Wilson BS, Hennessy RJ, Polak JM (1985) Chromogranin: A newly recognized marked for endocrine cells of the human gastrointestinal tract. Gastroenterology 89:1366–1373
Falkensammer G, Fischer-Colbrie R, Winkler H (1985) Biogenesis of chromaffin granules: incorporation of sulfate into chromogranin B and into a proteoglycan. J Neurochem 45:1475–1480
Fischer-Colbrie R, Frischenschlager I (1985) Immunological characterization of secretory proteins of chromaffin granules: chromogranins A, chromogranins B and enkephalin-containing peptides. J Neurochem 44:1854–1861
Fischer-Colbrie R, Schober M (1987) Isolation and characterization of chromogranins A, B and C from bovine chromaffin granules and a rat pheochromocytoma. J Neurochem 48:262–270
Fischer-Colbrie R, Lassmann H, Hagn C, Winkler H (1985) Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissue. Neuroscience 16:542–555
Fischer-Colbrie R, Hagn C, Kilpatrick L, Winkler H (1986) Chromogranin C: a third component of the acidic proteins in chromaffin granules. J Neurochem 47:318–321
Gould VE, Linnoila RI, Memoli VA, Warren WH (1983) Neuroendocrine cells and neuroendocrine neoplasms of the lung. Pathol Annu 18:287–330
Hagn C, Schmid KW, Fischer-Colbrie R, Winkler H (1986) Chromogranin A, B and C in adrenal medulla and endocrine tissues. Lab Invest 55:405–411
Helle KB (1966) Some chemical and physical properties of the soluble protein fraction of bovine adrenal chromaffin granules. Mol Pharmacol 2:298–310
Hogue-Angeletti R, Hickey WF (1985) A neuroendocrine marker in tissues of the immune system. Science 230:89–90
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
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
Lloyd RV, Wilson BS (1983) Specific endocrine tissue marker defined by a monoclonal antibody. Science 222:628–630
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Nash SV, Said JW (1986) Gastroenteropancreatic neuroendocrine tumors. Am J Clin Pathol 86:415–422
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
O'Connor DT, Burton D, Deftos LJ (1983a) Immunoreactive human chromogranin A in diverse polypeptide hormone producing human tumors and normal endocrine tissues. J Clin Endocrinol Metab 57:1084–1086
O'Connor DT, Burton D, Deftos LJ (1983b) Chromogranin A: immunohistology reveals its universal occurrence in normal polypeptide hormone producing endocrine glands. Life Sci 33:1657–1663
O'Farrel PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007
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
Rosa P, Fumagalli G, Zanini A, Huttner WB (1985) 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
Rosa P, Hille A, Lee RWH, Zanini A, De Camilli P, Huttner WB (1985) 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
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. Reg Peptides 16:217–233
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 tumours. Hum Pathol 16:236–240
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 Path in press
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 (in press)
Smith WD, Kirshner N (1967) A specific soluble protein from the catecholamine storage vesicles of bovine adrenal medulla: purification and chemical characterization. Mol Pharmacol 3:52–62
Smith AD, Winkler H (1967) Purification and properties of an acidic protein from chromaffin granules of bovine adrenal medulla. Biochem J 103:483–492
Somogyi P, Hodgson AJ, De Potter RW, Fischer-Colbrie R, Schober M, Winkler H, Chubb IW (1984) Chromogranin immunoreactivity in the central nervous system: immunochemical characterization, distribution and relationship to catecholamine and enkephalin pathways. Brain Res Rev 8:193–230
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
Walts AE, Said JW, Shintaku IP, Lloyd RV (1985) Chromogranin as a marker of neuroendocrine cells in cytologic material - an immunocytochemical study. Am J Clin Pathol 84:273–277
Williams ED, Sandler M (1963) The classification of carcinoid tumours. Lancet 1:238–239
Wilson BS, Lloyd RV (1984) Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol 115:458–468
Winkler H (1976) The composition of adrenal chromaffin granules: an assessment of controversial results. Neuroscience 1:65–80
Winkler H, Apps DK, Fischer-Colbrie R (1986) The molecular function of adrenal chromaffin granules: established facts and unresolved topics. Neuroscience 18:261–290
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
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Weiler, R., Feichtinger, H., Schmid, K.W. et al. Chromogranin A and B and secretogranin II in bronchial and intestinal carcinoids. Vichows Archiv A Pathol Anat 412, 103–109 (1987). https://doi.org/10.1007/BF00716181
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DOI: https://doi.org/10.1007/BF00716181