Expression of chromogranins A, B, and C (secretogranin II) in human adrenal medulla and in benign and malignant pheochromocytomas An immunohistochemical study with region‐specific antibodies

In a recent immunohistochemical study of pheochromocytomas, a difference was observed between benign and malignant pheochromocytomas in their expression in different parts of the chromogranin (Cg) A molecule. The purpose of the present study was to extend the investigations by including two other members of this Cg family, CgB and C. Twenty‐five patients operated on for clinicopathologically benign pheochromocytomas, and four for metastasizing pheochromocytomas, were studied. Expression of the different Cg regions was studied immunohistochemically by means of region‐specific antibodies: four raised against CgA epitopes, five against CgB, and two against CgC. Adrenal medulla parenchyma from three surgical adrenalectomy specimens was used as non‐neoplastic control. All cells of normal adrenal medulla were immunoreactive to all 11 region‐specific Cg antibodies. In the pheochromocytomas, variations in the expression pattern occurred, but no significant quantitative differences were noted between benign and malignant tumours. Nevertheless, in all four malignant pheochromocytomas, the antibodies raised against the C‐terminal regions of both CgB and CgC visualised a noticeable population of large spindle‐shaped tumour cells, characterised by elongated processes. This cell type occurred in all four malignant pheochromocytomas but only in one benign tumour. Their structure and immunoreactivity differed from those of the sustentacular cells in the pheochromocytoma parenchyma. The use of region‐specific antibodies raised against epitopes in the C‐terminal region of CgB and CgC can facilitate the diagnosis of malignant pheochromocytoma.

[1]  Moses Rodriguez,et al.  Multiple sclerosis: a unique immunopathological syndrome of the central nervous system , 2004, Springer Seminars in Immunopathology.

[2]  E. Bonifacio,et al.  Six months of gluten-free diet do not influence autoantibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes. , 2003, The Journal of clinical endocrinology and metabolism.

[3]  M. Stridsberg,et al.  Chromogranin A in the Human Gastrointestinal Tract: An Immunocytochemical Study with Region-specific Antibodies , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[4]  D. O'Connor,et al.  Malignant and Benign Pheochromocytoma , 2002 .

[5]  M. Stridsberg,et al.  Region-specific Antibodies to Chromogranin B Display Various Immunostaining Patterns in Human Endocrine Pancreas , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[6]  L. Thompson Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) to Separate Benign From Malignant Neoplasms: A Clinicopathologic and Immunophenotypic Study of 100 Cases , 2002, The American journal of surgical pathology.

[7]  D. Aunis,et al.  Chromogranins: Current Concepts , 2002 .

[8]  S. Asa,et al.  Prediction of malignant behavior of pheochromocytomas and paragangliomas using immunohistochemical techniques , 2002, Endocrine pathology.

[9]  D. O'Connor,et al.  Malignant and benign pheochromocytoma: chromaffin granule transmitters and the response to medical and surgical treatment. , 2002, Annals of the New York Academy of Sciences.

[10]  K. Wucherpfennig Insights into autoimmunity gained from structural analysis of MHC-peptide complexes. , 2001, Current opinion in immunology.

[11]  A. Ghezzi,et al.  Neurological manifestations of gastrointestinal disorders, with particular reference to the differential diagnosis of multiple sclerosis , 2001, Neurological Sciences.

[12]  E. Wilander,et al.  Chromogranin A in Human Neuroendocrine Tumors: An Immunohistochemical Study With Region-Specific Antibodies , 2001, The American journal of surgical pathology.

[13]  T. Olsson,et al.  Curative effects of recombinant human Interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis , 2001, Journal of Neuroimmunology.

[14]  M. Stridsberg,et al.  Selective Processing of Chromogranin A in the Different Islet Cells in Human Pancreas , 2001, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[15]  G. Prud’homme Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or inflammatory cytokine inhibitors , 2000, The journal of gene medicine.

[16]  H. Bruining,et al.  Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases? , 2000, The Journal of pathology.

[17]  A. Laslop,et al.  Levels and molecular properties of secretoneurin-immunoreactivity in the serum and urine of control and neuroendocrine tumor patients. , 2000, The Journal of clinical endocrinology and metabolism.

[18]  D. Aunis,et al.  Chromogranins: current concepts. Structural and functional aspects. , 2000, Advances in experimental medicine and biology.

[19]  A. Laslop,et al.  Proteolytic processing of chromogranins. , 2000, Advances in experimental medicine and biology.

[20]  K. Buschard,et al.  Gluten‐free diet prevents diabetes in NOD mice , 1999, Diabetes/metabolism research and reviews.

[21]  L. Castilla-Guerra,et al.  Expression of neuropeptides and other neuroendocrine markers in human phaeochromocytomas , 1999, Neuropeptides.

[22]  D. O'Connor,et al.  Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist. , 1997, The Journal of clinical investigation.

[23]  M. Stridsberg,et al.  Chromogranin A and chromogranin B are sensitive circulating markers for phaeochromocytoma. , 1997, European journal of endocrinology.

[24]  W. Barbeau Interactions between dietary proteins and the human system: implications for oral tolerance and food-related diseases. , 1997, Advances in experimental medicine and biology.

[25]  T. Stephenson,et al.  Does cryptic gluten sensitivity play a part in neurological illness? , 1996, The Lancet.

[26]  Tomas Olsson,et al.  Protracted, relapsing and demyelinating experimental autoimmune encephalomyelitis in DA rats immunized with syngeneic spinal cord and incomplete Freund's adjuvant , 1995, Journal of Neuroimmunology.

[27]  A. Laslop,et al.  Secretogranin II: Molecular properties, regulation of biosynthesis and processing to the neuropeptide secretoneurin , 1995, Progress in Neurobiology.

[28]  A. Cooke,et al.  Tolerance Induction as a Therapeutic Strategy for the Control of Autoimmune Endocrine Disease in Mouse Models , 1995, Immunological reviews.

[29]  J. Bach,et al.  Insulin-dependent diabetes mellitus as an autoimmune disease. , 1994, Endocrine reviews.

[30]  R. Kirchmair,et al.  Secretoneurin releases dopamine from rat striatal slices: A biological effect of a peptide derived from secretogranin II (chromogranin C) , 1993, Neuroscience.

[31]  F. Dagnaes-hansen,et al.  Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice , 1993, British Journal of Nutrition.

[32]  J. Polak Diagnostic histopathology of neuroendocrine tumours , 1993 .

[33]  E. Marliss,et al.  Conference summary: diet as an environmental factor in development of insulin-dependent diabetes mellitus. , 1991, Canadian journal of physiology and pharmacology.

[34]  D. Aunis,et al.  Chromostatin, a 20-amino acid peptide derived from chromogranin A, inhibits chromaffin cell secretion. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Hewson Dc Is there a role for gluten-free diets in multiple sclerosis? , 1984 .

[36]  Jones Lt,et al.  Gluten antibodies in patients with multiple sclerosis. , 1984 .

[37]  D. Hopwood,et al.  JEJUNAL MORPHOLOGY IN MULTIPLE SCLEROSIS , 1979, The Lancet.

[38]  J. Twomey,et al.  DIET AND MULTIPLE SCLEROSIS , 1974 .

[39]  W. N. Bailey An expression for , 1953 .