Skip to main content
SpringerLink
Log in

Immunocytochemical demonstration of intermediate filament cytoskeleton proteins in human endocrine tissues and (neuro-) endocrine tumours

  • Published:
Virchows Archiv A Aims and scope Submit manuscript

Summary

The presence and distribution of intermediate filament proteins, such as cytokeratins, vimentin, neurofilament proteins and glial fibrillary acidic protein were assessed immunohistochemically in pituitary adenomas, medullary thyroid carcinomas, endocrine pancreatic tumours, gastric, intestinal and bronchial carcinoids, parathyroid adenomas, pheochromocytomas, paragangliomas and related non-neoplastic tissues. In some cases, immunohistochemical results were correlated with cytoskeletal proteins as analysed by SDS-polyacrylamide gel electrophoresis. Cytokeratin antibodies with broad range of immunoreactivity (i.e. to murine liver cytokeratin component D) reacted with epithelial cells in all non-neoplastic endocrine tissues and related neuroendocrine tumours studied, except for adrenal medulla, pheochromocytoma and paraganglioma, independently of hormone production and biological behaviour. In contrast, antibodies to epidermis-derived cytokeratins failed to stain endocrine tissues and tumours. Paranuclear cytokeratin accumulations were seen in bronchial, gastric, and intestinal carcinoids and seem to be a common feature of neuroendocrine tumours. One-and two-dimensional SDS-polyacrylamide gel electrophoresis of non-neoplastic endocrine tissues and related tumours revealed two major keratin polypeptides corresponding to cytokeratins No. 8 and 18 of the cytokeratin catalog of human cells (Moll et al. 1982). According to this cytokeratin polypeptide composition, endocrine tissues and related tumours conform to the “simple type” of epithelia. Vimentin-related immunoreactivity was restricted to stromal cells and to folliculo-stellate cells in normal pituitary gland, Schwann cells in carcinoids and satellite cells in normal adrenal medulla and in pheochromocytomas. Neurofilament protein- (70 kD)-antibodies only stained nerve fibers in normal tissues and at the periphery of carcinoid tumour cell complexes, and, to a variable degree, cells in nontumorous adrenal medulla, pheochromocytomas and paragangliomas. Furthermore, neurofilament reactivity was observed along with cytokeratin expression in two bronchial carcinoids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Altmannsberger M, Osborn M, Kaeser H, Droese M, Weber K, Schauer A (1983) Neurofilamentproteine in Neuroblastomen and APUDomen. Verh Dtsch Ges Pathol 67:602

    Google Scholar 

  • Atwal OS, Pemsingh RS (1984) Occurrence of Mallory body-like inclusions in parathyroid chief cells of ozone-treated dogs. J Pathol 142:169–176

    Google Scholar 

  • Bassewitz DB von, Roessner A, Grundmann E (1982) Intermediate-sized filaments in cells of normal human colon mucosa, adenomas and carcinomas. Pathol Res Pract 175:238–255

    Google Scholar 

  • Berger G, Berger F, Bejui F, Bouvier R, Rochet M, Feroldi J (1984) Bronchial carcinoid with fibrillary inclusions related to cytokeratins: an immunohistochemical and ultrastructural study with subsequent investigation of 12 foregut APUDomas. Histopathol 8:245–252

    Google Scholar 

  • Bignami A, Raju T, Dahl D (1982) Localization of vimentin, the nonspecific intermediate filament protein, in embryonal glia and in early differentiating neurons. Dev Biol 91:286–295

    Google Scholar 

  • Blobel GA, Moll R, Franke WW, Vogt-Moykopf I (1984) Cytokeratins in normal lung and lung carcinomas. I Adenocarcinomas, squamous cell carcinomas and cultured cell lines. Virchow Arch (Cell Pathol) 45:407–420

    Google Scholar 

  • Blobel GA, Gould VE, Moll R, Lee I, Huszar M, Geiger B, Franke WW (1985) Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms. Lab Invest 52:39–51

    Google Scholar 

  • Carstens PHB, Broghamer WL (1977) Duodenal carcinoid with cytoplasmic whorls of microfilaments. J Pathol 124:235

    Google Scholar 

  • Cooper D, Schermer A, Tung-Tien Sun (1985) Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: Strategies, applications and limitations. Lab Invest 52:243–256

    Google Scholar 

  • Crabbe MI (1985) Partial sequence homologies between cytoskeletal proteins, c-myc, Rous sarcoma virus and adenovirus proteins, trans ducin and beta- and gamma-crystallins. Biosci Rep 5:167–174

    Google Scholar 

  • Denk H, Radaszkiewicz T, Weirich E (1977) Pronase pretreatment of tissue sections enhances sensitivity of the unlabeled antibody (PAP) technique. J Immunol Meth 15:163–167

    Google Scholar 

  • Denk H, Franke WW, Eckerstorfer R, Schmid E, Kerjaschki D (1979) Formation and involution of Mallory bodies (“alcoholic hyalin”) in murine and human liver revealed by immunofluorescence microscopy with antibodies to prekeratin. Proc Natl Acad Sci USA 76:4412–4116

    Google Scholar 

  • Denk H, Franke WW, Dragosics B, Zeiler I (1981) Pathology of cytoskeleton of liver cells: demonstration of Mallory bodies (alcoholic hyalin) in murine and human hepatocytes by immunofluorescence microscopy using antibodies to cytokeratin polypeptides from hepatocytes. Hepatology 1:9–20

    Google Scholar 

  • Denk H, Krepler R, Artlieb U, Gabbiani G, Rungger-Braendle E, Leoncini P, Franke WW (1983) Proteins of intermediate filaments. An immunohistochmical and biochemical approach to the classification of soft tissue tumors. Am J Pathol 110:193–208

    Google Scholar 

  • Draeger UC, Edwards DL, Kleinschmidt I (1983) Neurofilaments contain Alpha-melanocyte-stimulating hormone (Alpha-MSH)-like immunoreactivity. Proc Natl Acad Sci USA 80:6408–6412

    Google Scholar 

  • Franke WW, Appelhans B, Schmid E, Freudenstein C, Osborn M, Weber K (1979) Identification and characterization of epithelial cells in mammalian tissue by immunofluorescence microscopy using antibodies to prekeratin. Differentiation 15:7–18

    Google Scholar 

  • Franke WW, Schiller DL, Moll R, Winter S, Schmid E, Engelbrecht I, Denk H, Krepler R, Platzer B (1981) Diversity of cytokeratins: Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol 153:933–960

    Google Scholar 

  • Hoefler H, Kasper M, Heitz PhU (1983) The neuroendocrine system of normal human appendix, ileum and colon, and in neurogenic appendicopathy. Virchows Arch A (Pathol Anat) 399:127–140

    Google Scholar 

  • Hoefler H, Auboeck L (1984) S-100-protein in Carcinoiden. Verh Dtsch Ges Pathol 68:86–91

    Google Scholar 

  • Hoefler H, Denk H (1984) Immunocytochemical demonstration of cytokeratin in gastrointestinal carcinoids and their probable precursor cells. Virchows Arch (Pathol Anat) 403:235–240

    Google Scholar 

  • Hoefler H, Denk H, Walter GF (1984a) Immunohistochemical demonstration of cytoskeleton-proteins in normal pituitary gland and in pituitary adenomas. Virchows Arch A (Pathol Anat) 404:359–368

    Google Scholar 

  • Hoefler H, Walter GF, Denk H (1984b) Immunohistochemistry of folliculo-stellate cells in normal human adenohypophyses and in pituitary adenomas. Acta Neuropathol 65:35–40

    Google Scholar 

  • Hoefler H, Kloeppel G, Heitz PhU (1984c) Combined production of mucus, amines and peptides by Goblet-cell carcinoids of the appendix and ileum. Pathol Res Pract 178:555

    Google Scholar 

  • Hoefler H, Kerl H, Rauch HJ, Denk H (1984d) Cutaneous neuroendocrine carcinoma (Merkel Cell Tumor): New immunocytochemical observations with diagnostic significance. Am J Dermatopathol 6:525–530

    Google Scholar 

  • Horvath E, Kovacs K (1978) Morphogenesis and significance of fibrous bodies in human pituitary adenomas. Virchows Arch B (Cell Pathol) 27:69–78

    Google Scholar 

  • Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques. J Histochem Cytochem 29:577–580

    Google Scholar 

  • Kahn HJ, Garrido A, Huang SN, Baumal R (1983) Intermediate filaments and tumor diagnosis. Lab Invest 49:4:509–510

    Google Scholar 

  • Lehto VP, Miettinen M, Dahl D, Virtanen I (1984) Bronchial carcinoid cells contain neural-type of intermediate filaments. Cancer 54:624–628

    Google Scholar 

  • Lehto VP, Miettinen M, Virtanen I (1985) A dual expression of cytokeratin and neurofilaments in bronchial carcinoid cells. Int J Cancer 35:421–425

    Google Scholar 

  • Miettinen M, Partanen S, Lehto VP (1983) Mediastinal tumors: Ultrastructural and immunohistochemical evaluation of intermediate filaments as diagnostic aids. Ultrastruct Pathol 4:337–342

    Google Scholar 

  • Miettinen M, Franssila K, Lehto VP, Passivuo R, Virtanen I (1984) Expression of intermediate filament proteins in thyroid gland and thyroid tumors. Lab Invest 50:262–270

    Google Scholar 

  • Miettinen M, Lehto VP, Dahl D, Virtanen I (1985a) Varying expression of cytokeratin and neurofilaments in neuroendocrine tumors of the human gastrointestinal tract. Lab Invest 52:429–436

    Google Scholar 

  • Miettinen M, Lehto VP, Virtanen I (1985b) Immunofluorescence microscopic evaluation of the intermediate filament expression of the adrenal cortex and medulla and their tumors. Am J Pathol 118:360–366

    Google Scholar 

  • Miettinen M, Clark R, Lehto VP, Virtanen I, Damjanov I (1985c) Intermediate-Filament proteins in parathyroid glands and parathyroid adenomas. Arch Pathol Lab Med 109:986–989

    Google Scholar 

  • Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratin in normal epithelia, tumors and cultured cells. Cell 31:11–24

    Google Scholar 

  • Moll R, Krepler R, Franke WW (1983) Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation 23:256–261

    Google Scholar 

  • Van Muijen GNP, Ruiter D, Ponec M, Huiskens-van der Mey C, Warnaar SO (1984) Monoclonal antibodies with different specificities against cytokeratins. Am J Pathol 114:9–17

    Google Scholar 

  • Nagle RB, McDaniel KM, Clark VA, Payne CM (1983) The use of antikeratin antibodies in the diagnosis of human neoplasms. Am J Clin Pathol 79:458–466

    Google Scholar 

  • Neumann PE, Horoupian DS, Goldman JE, Hess MA (1984) Cytoplasmic filaments of Crooke's hyaline change belong to cytokeratin class. Am J Pathol 116:214–222

    Google Scholar 

  • Osborn M, Franke WW, Weber K (1980) Direct demonstration of the presence of two immunologically distinct intermediate-sized filament systems in the same cell by double immunofluorescence microscopy. Exp Cell Res 125:37–42

    Google Scholar 

  • Osborn M, Geisler N, Shaw G, Sharp G, Weber K (1982) Intermediate filaments. Cold Spring Harbor Symp Quant Biol 46:413–429

    Google Scholar 

  • Osborn M, Weber K (1983) Biology of Disease. Tumor diagnosis by intermediate filament typing: A novel tool for surgical pathology. Lab Invest 48:372–394

    Google Scholar 

  • Pearse AGE (1980) The APUD concept and hormone production. Clinics Endocrinol Metabol 9:211–222

    Google Scholar 

  • Permanetter W, Nathrath WBJ, Loehrs U (1982) Immunohistochemical analysis of thyroglobulin and keratin in benign and malignant thyroid tumours. Virchows Arch A (Pathol Anat) 398:211–228

    Google Scholar 

  • Racadot J, Oliver L, Porcile E, De Grye C, Klotz HP (1964) Adenome hypophysaire de type “mixte” avec symptomatologie acromegalique. II. Etude au microscope optique et au microscope electronique. Ann Endocrinol (Paris) 25:503–507

    Google Scholar 

  • Ramaekers FCS, Puts JJG, Moesker O, Kant A, Huysmans A, Haag D, Jap PHK, Herman CJ, Vooijs CP (1983) Antibodies to intermediate filament proteins in the immunohistochemical identification of human tumours: an overview. Histochem J 15:691–700

    Google Scholar 

  • Said JW, Nash G, Tepper G, Banks-Schlegel S (1983) Keratin proteins and carcinoembryonic antigen in lung carcinoma: An immunoperoxidase study of fifty-four cases, with ultrastructural correlations. Human Pathol 14:70–76

    Google Scholar 

  • Schlegel R, Banks-Schlegel S, McLeod J, Pinkus GS (1980) Immunoperoxidase localization of keratin in human neoplasms. Am J Pathol 101:41–49

    Google Scholar 

  • Schubart UK, Fields KL (1984) Identification of a calcium-regulated insulinoma cell phosphoprotein as an islet cell keratin. J Cell Biol 98:1001–1009

    Google Scholar 

  • Sternberger LA (1979) The unlabeled antibody peroxidase-antiperoxidase (PAP) method. In: Sternberger LA (ed) Immunocytochemistry. John-Wiley, New York, pp 104–169

    Google Scholar 

  • Trojanowski JQ, Lee VMY (1983) Anti-neurofilament monoclonal antibodies: reagents for the evaluation of human neoplasms. Acta Neuropathol 59:155–159

    Google Scholar 

  • Trojanowski JQ, Lee VMY (1985) Expression of neurofilament antigen by normal and neoplastic human adrenal chromaffin cells. New Engl J Med 313:101–104

    Google Scholar 

  • Virtanen I, Lehto VP, Lehtonen E, Vartio T, Stenman S (1981) Expression of intermediate filaments in cultured cells. Cell Sci 50:45–63

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, University of Graz, School of Medicine, Auenbruggerplatz 25, A-8036, Graz, Austria

    H. Hoefler, H. Denk, E. Lackinger & G. Helleis

  2. Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, England

    J. M. Polak

  3. Department of Pathology, University of Basel, School of Medicine, Switzerland

    Ph. U. Heitz

Authors
  1. H. Hoefler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Denk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Lackinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Helleis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. M. Polak
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ph. U. Heitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoefler, H., Denk, H., Lackinger, E. et al. Immunocytochemical demonstration of intermediate filament cytoskeleton proteins in human endocrine tissues and (neuro-) endocrine tumours. Vichows Archiv A Pathol Anat 409, 609–626 (1986). https://doi.org/10.1007/BF00713428

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00713428

Key words

Search

Navigation