Virchows Archiv B

, 10:93 | Cite as

The genesis of apudamyloid in endocrine polypeptide tumours: histochemical distinction from immunamyloid

  • A. G. E. Pearse
  • S. W. B. Ewen
  • J. M. Polak


The amyloid material in a series of seven endocrine polypeptide tumours (Apudomas) has been compared, in a variety of histochemical tests, with that present in two unselected cases of secondary amyloid. Significant differences include the absence, from apudamyloid, of tryptophan and tyrosine.

The N-terminal immunoglobulin light chain sequence hypothesis of Glenneret al. (1971), which derives secondary amyloid fibril protein from this source, is strongly supported by histochemical evidence. Absence of the two aromatic amino acids from apudamyloids indicates a different source for their fibril protein.

It is suggested that in the case of insulinomas the fibril protein is derived from C-peptide chains and that similar products (prohormone derivatives or amine-binding granule protein derivatives) are responsible for other endocrine tumour amyloids. The hyaline materials deposited in abnormal isletβ cells, and pituitary hyaline basophils (ACTH-secreting Crooke cells), may clearly have a similar type of origin.

The autofluorescence of immune amyloid has been shown to be due to oxidation of some of its tryptophan residues toN′-formylkynurenine. The mechanism by which this occurs is unknown but the participation of tryptophan pyrrolase is presumed.


Tryptophan Aromatic Amino Acid Medullary Thyroid Carcinoma Parathyroid Adenoma Amyloid Fibril 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adams, J. B.: Linkage of carbohydrate to hydroxyamino acids in mucopolysaccharides and mucoproteins. Biochem. J.97, 345–352 (1965).PubMedGoogle Scholar
  2. Albores-Saavedra, J., Rose, G. G., Ibanez, M. L., Russell, W. O., Grey, C. E., Dmochowski, L.: The amyloid in solid carcinoma of the thyroid gland-Staining characteristics, tissue culture and electron microscopic observations. Lab. Invest.13, 77–93 (1964).PubMedGoogle Scholar
  3. Benditt, E. P., Lagunoff, D., Eriksen, N., Iseri, O. A.: Amyloid: Extraction and preliminary characteristics of some proteins. Arch. Path.74, 323–330 (1962).PubMedGoogle Scholar
  4. Capella, C., Solcia, E.: Optical and electron microscopical study of cytoplasmic granules in human carotid body, carotid body tumours and jugulare tumours. Virchows Arch. Abt. B7, 37–53 (1971).Google Scholar
  5. Chance, R. E., Ellis, R. M., Bromer, W. W.: Porcine proinsulin: characterization and amino acid sequence. Sciene, N.Y.161, 165–167 (1968).Google Scholar
  6. Cohen, A. S.: Preliminary chemical analysis of partially purified amyloid fibrils. Lab. Invest.15, 66–83 (1966).Google Scholar
  7. Cunningham, W. L., Simkin, J. L.: Studies on glycopeptide derived from acidic glycoproteins of guinea-pig serum. Biochem. J.99, 434 442 (1966).PubMedGoogle Scholar
  8. Eanes, E. D., Glenner, G. G.: X-ray diffraction studies on amyloid filaments. J. Histochem. Cytochem.16, 673–677 (1968).PubMedGoogle Scholar
  9. Eppinger, H.: Zur Chemie der Amyloidenentartung. Biochem. Z.127, 107 (1922).Google Scholar
  10. Feyrter, F.: Über diffuse endokrine epitheliale Organe. Leipzig: J. A. Burth 1938.Google Scholar
  11. Feyrter, F.: Über die peripheren endokrinen (parakrinen) Drüsen des Menschen, 2. Aufl. Wien-Düsseldorf: W. Maudrich 1953.Google Scholar
  12. Feyrter, F.: Die Peripheren Endokrinen (Parakrinen) Drüsen. In: Kaufmann-Staemmler, Lehrbuch der Speziellen Pathologischen Anatomie, 11. u. 12. Aufl., S. 653–700. Berlin: de Gruyter and Co. 1969.Google Scholar
  13. Glenner, G. G., Terry, W., Harada, M., Isersky, G., Page, D.: Amyloid fibril proteins: Proof of homology with immunoglobulin light chains by sequence analyses. Science, N.Y.172, 1150–1151 (1971).Google Scholar
  14. Goessner, W.: Vergleichende histochemische Untersuchungen über die Proteinkomponente von Amyloid, Hyalin und Kollagen. Histochemie2, 199–216 (1961).PubMedCrossRefGoogle Scholar
  15. Gonzalez-Licea, A., Hartmann, W. H., Yardley, J. H.: Medullary carcinoma of the thyroid. Ultrastructural evidence of its origin from the parafollicular cell and its possible relation to carcinoid tumours. Amer. J. clin. Path.49, 512–520 (1968).Google Scholar
  16. Greengard, Olga, Feigelson, P.: The purification and properties of liver tryptophan pyrrolase. J. biol. Chem.237, 1903–1913 (1962).PubMedGoogle Scholar
  17. Hazard, J. B., Hawk, W. A., Crile, G. Jr.: Medullary (solid) carcinoma of the thyroid. A clinicopathologic entity. J. clin. Endocr.37, 205–209 (1959).Google Scholar
  18. Knox, W. E., Mehler, A. H.: The conversion of tryptophan to kynurenine in liver. I. The coupled tryptophan peroxidase-oxidase system forming formylkynurenine. J. biol. Chem.187, 419–430 (1950).PubMedGoogle Scholar
  19. Ko, A. S. C., Smyth, D. G., Markussen, J., Sundby, F.: The amino acid sequence of the C-peptide of human proinsulin. Europ. J. Biochem.20, 190–199 (1971).PubMedCrossRefGoogle Scholar
  20. Kronman, M. J., Holmes, L. G.: The fluorescence of native, denatured and reduced-denatured proteins. Photochem. Photobiol.14, 113–134 (1971).CrossRefGoogle Scholar
  21. Le Douarin, N., Le Lièvre, C.: Démonstration de l’origine neural des cellules à calcitonine du corps ultimobranchial chez l’embryon de Poulet. C. R. Acad. Sci. (Paris), Sér. D.270, 2857–2860 (1970).Google Scholar
  22. Milstein, C. P., Deverson, E. V.: The amino acid sequence of a human kappa light chain. Biochem. J.132, 945–958 (1971).Google Scholar
  23. Müller, M.: Etude clinique et anatomo-pathologique de 31 carcinomes médullaries à stroma amyloide de la thyroide. Schweiz. med. Wschr.99, 433–439 (1969).PubMedGoogle Scholar
  24. Murphy, W. H., Gottschalk, A.: Studies on mucoproteins. VII. The linkage of the prosthetic group to aspartic and glutamic acid residues in bovine submaximmary gland mucoprotein. Biochim. biophys. Acta (Amst.)52, 349–360 (1961).CrossRefGoogle Scholar
  25. Paloyan, E., Scanu, A., Straus, F. H., Pickleman, J. R., Paloyan, D.: Familial pheochromocytoma, medullary thyroid carcinoma and parathyroid adenomas. J. Amer. med. Ass.214 1443–1447 (1970).CrossRefGoogle Scholar
  26. Pearse, A. G. E.: The hypophysis in rheumatoid arthritis. Lancet (1950)I, 954.Google Scholar
  27. Pearse, A. G. E.: Cytological and cytochemical investigations on the foetal and adult hypophysis in various physiological and pathological states. J. Path. Bact.65, 355–370 (1953).PubMedCrossRefGoogle Scholar
  28. Pearse, A. G. E.: Histochemistry, theoretical and applied, 2nd ed. p. 284. London: J. & A. Churchill 1960.Google Scholar
  29. Pearse, A. G. E.: Common cytochemical properties of cells producing polypeptide hormones, with particular reference to calcitonin and the C cells. Vet. Rec.79, 587–590 (1966).PubMedGoogle Scholar
  30. Pearse, A. G. E.: Common cytochemical and ultrastructural characteristics of cells producing polypeptide hormones (The APUD Series) and their relevance to thyroid and ultimobranchial C cells. Proc. ray. Soc. B170, 71–80 (1968a).Google Scholar
  31. Pearse, A. G. E.: Histochemistry, theoretical and applied, 3rd ed., vol. 1. London: J. & A. Churchill 1968b.Google Scholar
  32. Pearse, A. G. E.: The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J. Histochem. Cytochem.17, 303–313 (1969).PubMedGoogle Scholar
  33. Pearse, A. G. E., Polak, Julia M.: Cytochemical evidence for the neural crest origin of mammalian ultimobranchial C cells. Histochemie27, 96–102 (1971a).PubMedCrossRefGoogle Scholar
  34. Pearse, A. G. E., Polak, Julia M.: Neural crest origin of the endocrine polypeptide cells of the gastrointestinal tract and pancreas. Gut12, 783–788 (1971b).PubMedCrossRefGoogle Scholar
  35. Pearse, A. G. E., Welsch, U.: Ultrastructural characteristics of the thyroid C cells in the summer, autumn and winter states of the hedgehog (Erinaceus europeaus L.) with some reference to other mammalian species. Z. Zellforsch.92, 596–609 (1968).PubMedCrossRefGoogle Scholar
  36. Phifer, R. F., Spicer, S. S.: Immunohistologic and immunopathologic demonstration of adrenocorticotrophic hormone in the pars intermedia of the adenohypophysis. Lab. Invest.23, 543–550 (1970).PubMedGoogle Scholar
  37. Phifer, R. F., Spicer, S. S., Orth, D. N.: Specific demonstration of the human hypophyseal cells which produce adrenocorticotropic hormone. J. clin. Endocr.31, 347–361 (1970).PubMedCrossRefGoogle Scholar
  38. Pirie, A.: Formation of N′-formylkynurenine in proteins from Lens and other sources by exposure to sunlight. Biochem. J.125, 203–208 (1971).PubMedGoogle Scholar
  39. Porta, A. E., Yerry, R., Scott, R. F.: Amyloidosis of funtioning islet cell adenomas of the pancreas. Amer. J. Path.41, 623–627 (1962).PubMedGoogle Scholar
  40. Pras, M., Nevo, Z., Schubert, M., Rotman, J., Matalon, R.: The significance of mucopolysaccharides in amyloid. J. Histochem. Cytochem.19, 443–448 (1971).PubMedGoogle Scholar
  41. Rost, F. W. D., Pearse, A. G. E.: An improved microspectrofluorimeter with automatic digital data logging: construction and operation. J. Microscopy94, 93–98 (1971).Google Scholar
  42. Satake, M., Okuyama, T., Ishihara, K., Schmid, K.: The carbohydrate-polypeptide linkages, the amino acid sequences of the peptides adjacent to some of these bonds, and the composition and size of the carbohydrate units of α1 acid glycoprotein. Biochem. J.95, 749–757 (1965).PubMedGoogle Scholar
  43. Schmidt, D. D., Arens, A.: Proinsulin vom Rind Isolierung. Eigenschaften und seine Aktivierung durch Trypsin. Hoppe-Seylers Z. physiol. Chem.349, 1157–1168 (1968).PubMedGoogle Scholar
  44. Shirahama, T., Cohen, A. S.: High resolution electron microscopic analysis of the amyloid fibril. J. Cell Biol.33, 679–708 (1967).PubMedCrossRefGoogle Scholar
  45. Smith, A. D., Winkler, H.: Purification and properties of an acidic protein from chromaffin granules of bovine adrenal medulla. Biochem. J.103, 483–492 (1967).PubMedGoogle Scholar
  46. Solcia, E., Vassallo, G., Capeila, C.: Selective staining of endocrine cells by basic dyes after acid hydrolysis. Stain. Technol.43, 257–263 (1968).PubMedGoogle Scholar
  47. Steiner, D. F., Oyer, P. E.: The biosynthesis of insulin and a probable precursor of insulin by a human islet adenoma. Proc. nat. Acad. Sci. (Wash.)57, 473–480 (1967).CrossRefGoogle Scholar
  48. Steiner, H.: Endokrin aktive Tumoren mit Amyloidstroma. Eine morphologische Untersuchung von Insulinomen und einem Calcitonin produzierenden Tumor. Virchows Arch. Abt. A.348, 170–180 (1969).CrossRefGoogle Scholar
  49. Štěrba, J.: Metastasierendes Bronchialkarzinoid mit Amyloid in Stroma. Zbl. allg. Path. path. Anat. 111, 555–561 (1968).Google Scholar
  50. Szijj, I., Csapó, Z., László, F. A., Kovács, K.: Medullary cancer of the thyroid gland associated with hypercorticism. Cancer. (Philad.)24, 167–173 (1969).CrossRefGoogle Scholar
  51. Teale, F. W. J.: The ultraviolet fluorescence of proteins in neutral solution. Biochem. J.76, 381–388 (1960).PubMedGoogle Scholar
  52. Williams, E. D., Brown, C. L., Doniach, I.: Pathological and clinical findings in a series of 67 cases of medullary carcinoma of the thyroid. J. clin. Path.19, 103–113 (1966).PubMedCrossRefGoogle Scholar
  53. Wolman, M.: Amyloid, its nature and molecular structure: Comparison of a new toluidine blue polarized light method with traditional procedures. Lab. Invest.25, 104–110 (1971).PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1972

Authors and Affiliations

  • A. G. E. Pearse
    • 1
  • S. W. B. Ewen
    • 1
  • J. M. Polak
    • 1
  1. 1.Department of HistochemistryRoyal Postgraduate Medical SchoolLondonEngland

Personalised recommendations