Histochemistry

, Volume 72, Issue 2, pp 161–171 | Cite as

Immunocytochemical identification of amyloid in formalin-fixed paraffin sections

  • T. Shirahama
  • M. Skinner
  • A. S. Cohen
Article
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Summary

Formalin-fixed paraffin sections of livers, spleens and kidneys from patients with primary, secondary and familial amyloidosis as well as from a casein-induced murine amyloid model were analysed by an immunocy-tochemical (unlabeled antibody enzyme) method utilizing antisera to amyloid-related proteins. All amyloid deposits of all amyloid types showed positive reactions with anti-AP of the respective species. Positive reaction of anti-human AA to human secondary amyloid deposits and of anti-mouse AA to the deposits of casein-induced murine amyloid was also observed, but there was no species cross reactivity. No significant deposition of the reaction products was produced by anti-immunoglobulin light chains on deposits of any amyloid type, or by anti-AA in the tissues from primary or familial amyloidosis. The results indicate that amyloid proteins AA and AP can survive as antigens through routine histologic preparation, that anti-AP can be a universal marker for deposits of any amyloid type within the same species, and that AA-type amyloid can be identified by this method while there may as yet be no feasible universal marker for the AL-type at present.

Keywords

Amyloidosis Positive Reaction Amyloid Deposit Amyloid Protein Histologic Preparation 
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.
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References

  1. Benditt EP, Eriksen N (1971) Chemical classes of amyloid substance. Am J Pathol 65:231–252Google Scholar
  2. Benson MD, Kleiner E (1980) Synthesis and secretion of serum amyloid protein A (SAA) by hepatocytes in mice treated with casein. J Immunol 124:495–499Google Scholar
  3. Cathcart ES, Shirahama T, Cohen AS (1967) Isolation and identification of a plasma component of amyloid. Biochim Biophys Acta 147:392–393Google Scholar
  4. Cohen AS (1967) Amyloidosis. N Engl J Med 277:522–530, 574–583, 628–638Google Scholar
  5. Cohen AS, Calkins E (1959) A light and electron microscopic study of human amyloid diesease of the kidney. Arthritis Rheum 2:70–71Google Scholar
  6. Cohen AS, Cathcart ES (1980) Amyloidosis. In: LoBue J (ed) Contemporary hematology and oncology. Plenum Press, New York, pp 243–276Google Scholar
  7. Cohen AS, Wegelius O (1980) Classification of amyloid: 1979–1980. Arthritis Rheum, 23:644–645Google Scholar
  8. Cornwell GG III, Natvig JB, Westermark P, Husby G (1978) Senile cardiac amyloid: demonstration of a unique fibril protein in tissue sections. J Immunol 120:1385–1388Google Scholar
  9. Costa PP, Figueira AS, Bravo FR (1978) Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy. Proc Natl Acad Sci USA 75:4499–4503Google Scholar
  10. Eriksen N, Ericsson LH, Pearsall N, Lagnoff D, Benditt EP (1976) Mouse amyloid protein AA: homology with nonimmunoglobulin protein of human and monkey amyloid substance. Proc Natl Acad Sci USA 73:964–967Google Scholar
  11. Fujihara S, Balow JE, Costa JC, Glenner GG (1980) Identification and classification of amyloid in formalin-fixed, paraffin-embedded tissue sections by the unlabeled immunoperoxidase method. Lab Invest 43:358–365Google Scholar
  12. Glenner GG (1980) Amyloid deposits and amyloidosis: the β-fibrilloses. N Engl J Med 302:1283–1292, 1333–1343Google Scholar
  13. Glenner GG, Costa PP, Freitas AF (eds) (1980) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, p 629Google Scholar
  14. Glenner GG, Terry W, Harada M, Isersky C, Page D (1971) Amyloid fibril proteins: proof of homology with immunoglobulin light chains by sequence analysis. Science 172:1150–1151Google Scholar
  15. Husby G, Natvig JB, Michaelsen TE, Sletten K Höst H (1973) Unique amyloid protein subunit common to different types of amyloid fibril. Nature 244:362–364Google Scholar
  16. Kyle RA, Bayrd ED (1975) Amyloidosis: review of 236 cases. Medicine 54:271–299Google Scholar
  17. Levin M, Franklin EC, Frangione B, Pras M (1972) The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. J Clin Invest 51:2773–2776Google Scholar
  18. Linder E, Anders RF, Natvig JB (1976) Connective tissue origin of the amyloid-related serum protein SAA. J Exp Med 144:1336–1346Google Scholar
  19. Linke RP, Geisel O, Eulitz M, Nathrath WBJ (1980) Idiopathic amyloidosis in the stone marten (Martes foina): identification of amyloid fibril proteins in tissue sections using the immunoperoxidase technique. Blut 41:465–468Google Scholar
  20. Livni N, Laufer A, Levo Y (1980) Demonstration of amyloid in murine and human secondary amyloidosis by the immunoperoxidase technique. J Pathol 132:343–348Google Scholar
  21. Mellors RC, Ortega LG (1956) Analytical pathology. III. New observations on the pathogenesis of glomerulonephritis, lipid nephrosis, periarteritis nodosa, and secondary amyloidosis in man. Am J Pathol 32:455–500Google Scholar
  22. Moyner K, Sletten K, Husby G, Natvig JB (1980) An unusually large (83 amino-acid residues) amyloid fibril protein-AA from a patient with Waldenstroms macroglobulinemia and amyloidosis. Scand J Immunol 11:549–554Google Scholar
  23. Osserman EF (1965) Amyloidosis and plasma cell dyscrasia. In: Grabar P, Miescher PA (eds) Immunopathology: IVth international symposium. Grune and Stratton, New York, pp 283–293Google Scholar
  24. Pepys MB, Dash AC, Munn EA, Feinstein A, Skinner M, Cohen AS, Gewurz H, Osmand AP, Painter RH (1977) Isolation of amyloid P-component (protein AP) from normal serum as a calcium-dependent binding protein. Lancet 1:1029–1031Google Scholar
  25. Pruzanski W, Katz A (1976) Clinical and laboratory findings in primary generalized and multiplemyeloma-related amyloidosis. Can Med Assoc J 114:906–909Google Scholar
  26. Puchtler H, Sweat F, Levine M (1962) On the binding of Congo red by amyloid. J Histochem Cytochem 10:355–364Google Scholar
  27. Shirahama T, Cohen AS (1973) An analysis of the close relationship of lyosomes to early deposits of amyloid. Ultrastructural evidence in experimental mouse amyloidosis. Am J Pathol 73:97–114Google Scholar
  28. Shirahama T, Skinner M, Cohen AS (1977) Immunocytochemical localization of amyloid protein AA in the “dense fibrillar inclusions” of the reticuloendothelial cells In: Bailey GW (ed) 35th Ann Proc Electron Microscopy Soc Am. Claitor's Publishing Division, Baton Rouge, Louisiana, pp 438–439Google Scholar
  29. Shirahama T, Skinner M, Cohen AS (1979) Nonfibrillar deposits of an amyloid protein AA-ractive substance. Fed Proc 38:1408Google Scholar
  30. Shirahama T, Skinner M, Cohen AS (1980a) Possible deposition in tissue of amyloid protein in a nonfibrillar form. In: Glenner GG, Costa PP, Freitas AF (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 278–282Google Scholar
  31. Shirahama T, Skinner M, Cohen AS (1980b) Identification and localization of amyloid by immunocytochemistry with antisera against amyloid-related proteins. Fed Proc 39:1020Google Scholar
  32. Skinner M, Cohen AS (1981) The prealbumin nature of the amyloid protein in familial amyloid polyneuropathy (FAP)—Swedish variety. Biochem. Biophys Res Commun 99:1326–1332Google Scholar
  33. Skinner M, Cathcart ES, Cohen AS, Benson MD (1974a) Isolation and identification by sequence analysis of experimentally induced guinea pig amyloid fibrils. J Exp Med 140:871–876Google Scholar
  34. Skinner M, Cohen AS, Shirahama T, Cathcart ES (1974b) P-component (pentagonal unit) of amyloid: isolation, characterization, and sequence analysis. J Lab Clin Med 84:604–614Google Scholar
  35. Skinner M, Pepys MB, Cohen AS, Heller LM, Lian JB (1980) Studies on amyloid protein AP. In: Glenner GG, Costa PP, Freitas AF (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 384–391Google Scholar
  36. Skinner M, Shirahama T, Benson MD, Cohen AS (1977) Murine amyloid protein AA in caseininduced experimental amyloidosis. Lab Invest 36:420–427Google Scholar
  37. Sletten K, Westermark P, Natvig JB (1976) Characterization of amyloid fibril proteins from medullary carcinoma of the thyroid J Exp Med 143:993–998Google Scholar
  38. Spark EC, Shirahama T, Skinner M, Cohen AS (1978) The identification of amyloid P-component (protein AP) in normal cultured human fibroblasts. Lab Invest 38:556–559Google Scholar
  39. Sternberger LA (1979) Immunocytochemistry, 2nd ed. John Wiley and Sons, New York, p 354Google Scholar
  40. Sternberger LA, Hardy PH Jr, Cuculis JJ Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333Google Scholar
  41. Thompson AR, Endield DL (1978) Human plasma P component isolation and characterization. Biochemistry 17:4304–4311Google Scholar
  42. Vassar PS, Culling CFA (1959) Fluorescent stains, with special reference to amyloid and connective tissues. Arch Pathol 68:487–498Google Scholar
  43. Vazquez JJ, Dixon FJ (1956) Immunohistochemical analysis of amyloid by the fluorescence technique. J Exp Med 104:727–736Google Scholar
  44. Wegelius O, Pasternack A (eds) (1976) Amyloidosis. Academic Press, New York, p 605Google Scholar
  45. Westermark P, Grimelius L, Polak JM, Larsson LI, VanNoorden S, Wilander E, Pearse AGE (1977) Amyloid in polypeptide hormone-producing tumors. Lab Invest 37:212–215Google Scholar
  46. Westermark P, Johansson B, Natvig JB (1979) Senile cardiac amyloidosis: existence of two different amyloid substances in the aging heart. Scand J Immunol 10:303–308Google Scholar
  47. Westermark P, Shirahama T, Skinner M, Cohen AS (1981) Amyloid P-component (protein AP) in localized amyloidosis as revealed by an immunocytochemical method. Histochemistry 71: 171–175Google Scholar
  48. Zucker-Franklin D (1976) Studies on, the cellular origin of the acid-soluble component of amyloid. In: Wegelius O, Pasternack A (eds) Amyloidosis. Academic Press, New York, pp 353–360Google Scholar
  49. Zucker-Franklin D, Franklin EC (1970) Intracellular localization of human amyloid by fluorescence and electron microscopy. Am J Pathol 59:23–42Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • T. Shirahama
    • 1
    • 2
    • 3
    • 4
    • 5
  • M. Skinner
    • 1
    • 2
    • 3
    • 4
    • 5
  • A. S. Cohen
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.The Arthritis Center of Boston UniversityBoston City HospitalBostonUSA
  2. 2.the Arthritis and Connective Tissue Disease SectionBoston City HospitalBostonUSA
  3. 3.the Thorndike Memorial Laboratory and Division of MedicineBoston City HospitalBostonUSA
  4. 4.the Evans Memorial Department of Clinical ResearchUniversity HospitalBostonUSA
  5. 5.the Department of MedicineBoston University School of MedicineBostonUSA

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