Abstract
Chromogranin A (CgA), pancreastatin (PST), intervening-peptide (IP) and WE-14 antisera were employed to investigate the proteolysis of CgA in 50 pituitary adenomas. All non-functioning (NF) pituitary tumours (n = 28) exhibited CgA immunoreactivity. PST, IP and WE-14 immunostaining was observed in 85%, 89% and 67%, respectively. CgA, PST and 1P immunostaining were comparable in the majority of NF tumours, while less intense WE-14 immunoreactivity was detected in a subpopulation of NF tumour cells. Approximately half of the functioning pituitary tumours expressed CgA immunoreactivity. Six of nine ACTH-secreting tumours displayed CgA and IP immunostaining; four of these tumours displayed PST immunoreactivity. WE-14 immunoreactivity was detected in one corticotroph tumour. Three of six growth hormone (GH) secreting tumours displayed CgA immunostaining, two exhibited PST and IP, and one exhibited WE-14 immunoreactivity. Clusters of WE-14 immunopositive cells were detected in one GH tumour. One of seven prolactinomas exhibited weak CgA immunostaining, while weak IP and WE-14 immunostaining was detected in an additional tumour. No PST immunostaining was detected in prolactinomas. Therefore CgA is a valuable marker of NF pituitary tumours, however it is a more sporadic marker of functioning adenomas. In general, the cellular pattern and intensities of CgA, PST and IP immunoreactivity were comparable in the majority of pituitary adenomas. In contrast, WE-14 immunostaining was observed in a subpopulation of tumour cells. The pathophysiological significance of the proteolysis of CgA to generate bioactive peptides in both NF and functioning pituitary adenomas remains to be established.
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DeStephano DB, Lloyd RV, Pike AM, Wilson BS. Pituitary adenomas: An immunohistochemical study of hormone production and chromogranin localisation. Am J Pathol 1984;116:464–472.
Lloyd RV, Cano M, Rosa P, Hille A, Huttner, WB. Distribution of chromogranin A and secretogranin I (chromogranin B) in neuroendocrine cells and tumours. Am J Pathol 1988;130:296–304.
Lloyd RV, Wilson BS, Kovacs K, Ryan N. Immunohistochemical localisation of chromogranin in human hypophyses and pituitary adenomas. Arch Pathol Lab Med 1985;109:515–517.
Deftos LJ, O'Connor DT, Wilson CB, Fitzgerald PA. Human pituitary tumours secrete chromogranin-A. J Clin Endocrinol Metab 1989;68:869–872.
Schmid KW, Kroll M, Hittmair A, Maier H, Totsch M, Gasser R, Finkenstett G, Hogue-Angeletti R, Fischer-Colbrie R. Chromogranin A and B in adenomas of the pituitary. An immunohistochemical study of 42 cases. Am J Surg Pathol 1991;15:1072–1077.
Jin L, Chandler WF, Smart JB, England BG, Lloyd RV. Differentiation of human pituitary adenomas determines the pattern of chromogranin/secretogranin messenger ribonucleic acid expression. J Clin Endocrinol Metab 1993;76:728–735.
Nobels FRE, Kwekkeboom DJ, Coopmans W, Hoekstra R, De Herder WW, Bouillon R, Lamberts SWJ. A comparison between the diagnostic value of gonadotrophins, alphasubunit, and chromogranin-A and their response to thyrotrophin-releasing hormone in clinically nonfunctioning, alphasubunit-secreting, and gonadotroph pituitary adenomas. J Clin Endocrinol Metab 1993;77:784–789.
Wiedmann B, Huttner WB. Synaptophysin and chromogranin/ secretogranins-widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumour diagnosis. Virch Arch B Cell Pathol 1989;58:95–121
O'Connor DT, Burton D, Deftos LJ. Immunoreactive human chromogranin A in diverse polypeptide hormone producing human tumours and normal endocrine tissues. J Clin Endocrinol Metab 1983;57:1084–1086
Winkler H, Fischer-Colbrie R. The chromogranins A and B: the first 25 years and future perspectives. Neuroscience 1992;49:497–528.
Iacengelo AL, Eiden LE. Chromogranin A: current status as a precusor for bioactive peptides and a granulogenic / sorting factor in the regulated secretory pathway. Regult Pep 1995;58:65–88
Arden SD, Rutherford NG, Guest PC, Curry WJ, Bailyes EM, Johnston CF, Hutton JC. The post-translational processing of chromogranin A in the pancreatic islet: involvement of the eukaryote subtilisin PC2. Biochem J 1994;298:521–528.
Tatemoto K, Efendic S, Mutt V, Makk G, Feistner G, Barchas J. Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 1986;326:476–478.
Aardal S, Helle KB. The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels. Regult Pept 1992;41:9–18.
Forsythe P, Curry WJ, Johnston CF, Harriott P, MacMahon J, Ennis M. The modulatory effects of WE-14 on histamine release from rat peritoneal mast cells. Inflammation Res 1997;46:S13–S14.
Barbosa JA, Gill BM, Takiyyuddin MA, O'Connor DT. Chromogranin A: posttranslational modi~cations in secretory granules. Endocrinology 1991;128:174–190.
Curry WJ, Johnston CF, Hutton JC, Arden SD, Rutherford NG, Shaw C, Buchanan KD. The tissue distribution of rat chromogranin A-derived peptides: evidence for differential processing from sequence specific antisera. Histochemistry 1991;96:531–538.
Watkinson A, Jonsson A-C, Davison M, Young J, Lee CM, Moore S, Dockray GJ. Heterogeneity of chromogranin A-derived peptides in bovine gut, pancreas and adrenal medulla. Biochem J 1991;276:471–479.
Gleeson CM, Curry WJ, Johnston CF, Buchanan KD. Occurrence of WE-14 and heterogenous chromogranin A-derived peptides in tissues of the human and bovine gastro-enteropancreatic system and in human neuroendocrine neoplasia. J Endocrinol 1996;151:409–420.
McGrath-Linden SJ, Johnston CF, O'Connor DT, Shaw C, Buchanan KD. Pancreastatin like immunoreactivity in human carcinoid disease. Regult Pept 1991;33:55–70.
Curry WJ, Shaw C, Johnston CF, Thim L, Buchanan KD. Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour. FEBS Lett 1992;301:319–321.
Klibanski A. Non secretory pituitary tumours. Endocrinol Metab Clin North Am 1987;16:793–804.
Ridgway EC, Klibanski A, Ladenson PW, Clemmons D, Beitins IZ, McArthur JW, Martorana MA, Zervas MT. Pure alpha-secreting pituitary adenomas. N Engl J Med 1981;304:1254–1259.
Saccomanno K, Gil del Alamo P, Bassetti M, Reza-Elahi F, Spada A. In vitro detection of glycoprotein production and secretion by human nonfunctioning pituitary adenomas. J Endocrinol Invest 1993;16:109–115.
Sautner D, Saeger W, Ludecke DK. Tumours of the sellar region mimicking pituitary adenomas. Exp Clin Encocrinol 1993;101:283–289.
Lloyd RV, Jin L, Qian X, Scheithauer BW, Young WF, Davis DH. Analysis of the chromogranin A post-translational cleavage product pancreastatin and prohormone convertases PC2 and PC3 in normal and neoplastic human pituitaries. Am J Pathol 1995;146:1188–1198.
Kovacs K, Horvath E, Ryan N, Ezrin C. Null cell adenoma of the human pituitary. Virchows Arch Pathol 1980;387:165–174.
Mbikay M, Seidah NG, Chretien M. From pro-opicmelanocortin to cance: possible role of convertases in neoplasia. Ann NY Acad Sci 1993;680:13–19
Takumi I, Steiner DF, Sanno N, Teramoto A, Osamura RY. Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and pituitary adenomas; analysis by immunohistochemistry, immunoelectron microscopy and laser scanning microscopy. Mod Pathol 1998;11:3232–3235
Muller L, Picart P, Garret A, Seidah NG, Tougard C. Immunocytochemical localization of the Prohormone Convertases PC1 and PC2 in Rat Prolactin Cells. J Histochem Cytochem 1998;46:101–108
Koeslag JH, Peter T, Saunders PT, Jabus A, Wessels. The chromogranins and the counter-regulatory hormones: do they make homeostatic sense? J Physiology 1999;517:643–649.
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Heaney, A.P., Curry, W.J., Pogue, K.M. et al. Immunohistochemical Evaluation of the Post-Translational Processing of Chromogranin A in Human Pituitary Adenomas. Pituitary 3, 67–75 (2000). https://doi.org/10.1023/A:1009949623054
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DOI: https://doi.org/10.1023/A:1009949623054