Summary
The occurrence of immunoreactive cystatin C (CC) in normal and neoplastic cells of the human pancreas and gut was investigated using an indirect streptavidin-biotin method on formaldehyde-fixed and paraffin-embedded tissues. Virtually all pancreatic islet cells and many neuroendocrine cells throughout the gastrointestinal tract showed strong CC immunoreactivity and a granular cytoplasmic staining pattern. All 14 endocrine pancreatic tumours (insulinomas, glucagonomas, gastrinomas and non-producing tumours), as well as 16 of 17 gut carcinoid tumours, were also strongly CC immunoreactive. In addition, non-endocrine epithelial cells of pancreatic ducts and the gastrointestinal mucosa and 20 of the 24 adenocarcinomas from these sites showed weak CC immunoreactivity. Thus, CC cannot be used as a reliable immunohistochemical marker for endocrine gastro-entero-pancreatic tumours despite the fact that the protein is strongly expressed in a majority of such tumours.
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Abrahamson M, Islam MQ, Szpirer J, Szpirer C, Levan G (1989) The human cystatin C gene (CST3), mutated in hereditary cystatin C amyloid angiopathy, is located on chromosome 20. Hum Genet 82:223–226
Abrahamson M, Olafsson I, Palsdottir A, Ulvsbäck M, Lundwall Å, Jensson O, Grubb A (1990) Structure and expression of the human cystatin C gene. Biochem J 268:287–294
Brzin J, Popovic T, Turk V (1984) Human cystatin C: a new protein inhibitor of cysteine proteinases. Biochem Biophys Res Commun 118:103–109
Cole T, Dickson PW, Esnard F, Averill S, Risbridger GP, Gauthier F (1989) The cDNA structure and expression analysis of the genes for the cysteine proteinase inhibitor cystatin C and for beta-2-microglobulin in rat brain. Eur J Biochem 186:35–42
Collins VP, Jacobsson B, Pettersson T, Carlström A (1986) Monoclonal antibodies to transthyretin. Scand J Clin Lab Invest 46:761–769
Dalböge H, Jensen EB, Töttrup H, Grubb A, Abrahamson M, Olafsson I, Carlsen S (1989) High-level expression of active human cystatin C inEscherichia coli. Gene 79:325–332
Eriksson B, Arnberg H, Öberg K, Hellman U, Lundqvist G, Wernstedt C, Wilander E (1990) A polyclonal antiserum against chromogranin A and B — a new sensitive marker for neuroendocrine tumors. Acta Endocrinol (Copenh) 122:145–155
Grimelius L, Wilander E (1980) Silver stains in the study of endocrine cells of the gut and pancreas. Invest Cell Pathol 3:3–12
Grubb A, Löfberg H (1982) Human gamma-trace, a basic microprotein: amino acid sequence and presence in the adenohypophysis. Proc Natl Acad Sci USA 79:3024–3027
Grubb A, Löfberg H (1985) Human gamma-trace: structure, function and clinical use of concentration measurements. Scand J Clin Lab Invest 45 [Suppl 177]:7–13
Jacobsson B (1989) In situ localization of transthyretin mRNA in adult human liver, choroid plexus and pancreatic islets and in endocrine tumours of the pancreas and gut. Histochemistry 91:299–304
Jacobsson B, Carlström A, Collins VP, Grimelius L (1989a) Trans-thyretin in endocrine pancreatic tumours. Am J Pathol 134:465–471
Jacobsson B, Collins VP, Grimelius L, Pettersson T, Sandstedt B, Carlström A (1989b) Transthyretin immunoreactivity in human and porcine liver, choroid plexus, and pancreatic islets. J Histochem Cytochem 37:31–37
Jacobsson B, Carlström A, Platz A, Collins VP (1990) Transthyretin messenger ribonucleic acid expression in the pancreas and in endocrine tumors of the pancreas and gut. J Clin Endocrinol Metab 71:875–880
Liddle CN, Reid WA, Kennedy JS, Miller ID, Horne CHW (1985) Immunolocalization of prealbumin: distribution in normal human tissues. J Pathol 146:107–113
Löfberg H, Grubb AO, Brun A (1981a) Human brain cortical neurons contain gamma-trace. Rapid isolation, immunohistochemical and physiochemical characterization of human gamma-trace. Biomed Res 2:298–306
Löfberg H, Strömblad LG, Grubb A, Olsson SO (1981b) Demonstration of gamma-trace in normal and neoplastic endocrine A-cells of the pancreatic islets: an immunohistological study of monkey, rat, and man. Biomed Res 2:527–535
Löfberg H, Nilsson KE, Strömblad L-G, Lasson Å, Olsson S-O (1982) Demonstration of gamma-trace in normal endocrine cells of the adrenal medulla and in phaeochromocytoma. An immunohistochemical study in monkey, dog and man. Acta Endocrinol (Copenh) 100:595–598
Löfberg H, Grubb A, Davidsson L, Kjellander B, Strömblad L-G, Tibblin S, Olsson S-O (1983) Occurrence of gamma-trace in the calcitonin-producing C-cells of simian thyroid gland and human medullary thyroid carcinoma. Acta Endocrinol (Copenh) 104:69–76
Löfberg H, Grubb AO, Jörnvall H, Möller CA, Strömblad L-G, Olsson S-O (1984) Gamma-trace in human pituitary adenomas. J Clin Endocrinol Metab 59:113–118
Miller ID, Reid WA, Liddle CN, Home CHW (1984) Immunolocalization of prealbumin as a marker for carcinoid tumours. JPathol 143:199–204
Möller CA, Löfberg H, Grubb AO, Olsson S-O, Davies ME, Barrett AJ (1985) Distribution of cystatin C (gamma-trace), an inhibitor of lysosomal cysteine proteinases in the anterior lobe of simian and human pituitary glands. Neuroendocrinol 41:400–404
Olafsson I, Löfberg H, Abrahamson M, Grubb A (1988) Production, characterization and use of monoclonal antibodies against the major extracellular human cysteine proteinase inhibitors cystatin C and kinogen. Scand J Clin Lab Invest 48:573–582
Sloan BF (1990) Catepsin B and cystatins: evidence for a role in cancer progression. Cancer Biol 1:137–152
Turk V, Bode W (1991) The cystatins: protein inhibitors of cysteine proteinases. FEBS Lett 285:213–219
Warfel AH, Zucker-Franklin D, Frangione B, Ghiso J (1987) Constitutive secretion of cystatin C (gamma-trace) by monocytes and macrophages and its downregulation after stimulation. J Exp Med 166:1912–1917
Wilson BS, Lloyd RV (1984) Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol 115:458–468
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Lignelid, H., Jacobsson, B. Cystatin C in the human pancreas and gut: An immunohistochemical study of normal and neoplastic tissues. Vichows Archiv A Pathol Anat 421, 491–495 (1992). https://doi.org/10.1007/BF01606878
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DOI: https://doi.org/10.1007/BF01606878