Skip to main content

Advertisement

SpringerLink
Log in

Analysis of Amyloid in Medullary Thyroid Carcinoma by Mass Spectrometry-Based Proteomic Analysis

  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Amyloid is a characteristic histologic feature in medullary thyroid carcinomas (MTC). We utilized a novel mass spectrometry-based proteomic analysis to determine if we could identify specific proteins associated with amyloid in MTC. We studied 9 MTC (1 multiple endocrine neoplasia type 2A, 1 familial MTC, and 7 sporadic). Laser microdissection was utilized to sample the amyloid which was then trypsin digested and evaluated by liquid chromatography electrospray tandem MS (LC-MS/MS) which identified the presence of amyloidogenic proteins in all cases of MTC. High levels of calcitonin were identified in all 9 cases of MTC. Secretogranin-1 was identified in 6 of 9 MTC. Calcitonin gene-related peptide was identified in 4 of 9 cases of MTC. LC-MS/MS proteomic analysis provides a rapid, highly specific, and sensitive method for identification of the specific type of amyloid in these endocrine tumors. This approach may allow classification of different forms of endocrine amyloid present in neuroendocrine tumors.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Vrana JA, Gamez JD, Madden BJ et al. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood 114(24):4957–4959, 2009.

    Article  CAS  PubMed  Google Scholar 

  2. Dasari S, Theis JD, Vrana JA et al. Clinical proteome informatics workbench detects pathogenic mutations in hereditary amyloidoses. J Proteome Res. 13(5):2352–23588, 2014

    Article  CAS  PubMed  Google Scholar 

  3. Vrana JA, Theis JD, Dasari S, et al. Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics. Haematologica. 99(7):1239–1247, 2014.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Sethi S, Vrana JA, Theis JD, Dogan A. Mass spectrometry based proteomics in the diagnosis of kidney disease. Curr Opin Nephrol Hypertens. 22(3):273–80, 2013.

    Article  CAS  PubMed  Google Scholar 

  5. Maleszewski JJ, Murray DL, Dispenzieri A, et al. Relationship between monoclonal gammopathy and cardiac amyloid type. Cardiovasc Pathol. 22(3):189–194, 2013.

    Article  CAS  PubMed  Google Scholar 

  6. Albores-Saavedra J, Rose GG, Ibanez ML et al. The amyloid in solid carcinoma of the thyroid gland: staining characteristics, tissue cultures and electron microscopic observations. Lab Invest 13:77–89, 1964.

    CAS  PubMed  Google Scholar 

  7. Meyer JS. Fine structure of two amyloid-forming medullary carcinomas of thyroid. Cancer 21(3):406–425, 1968.

    Article  CAS  PubMed  Google Scholar 

  8. Meyer JS, Hutton WE, Kenny AD. Medullary carcinoma of thyroid gland. Subcellular distribution of calcitonin and relationship between granules and amyloid. Cancer 31(2):433–41, 1973

    Article  CAS  PubMed  Google Scholar 

  9. Arnal-Monreal FM, Goltzman D, Knaack J, Wang NS, Huang SN. Immunohistologic study of thyroidal medullary carcinoma and pancreatic insulinoma. Cancer 40(3):1060–1070, 1977.

    Article  CAS  PubMed  Google Scholar 

  10. Sletten K, Westermark P, Natvig JB. Characterization of amyloid fibril proteins from medullary carcinoma of the thyroid. J Exp Med 143(4):993–998, 1976.

    Article  CAS  PubMed  Google Scholar 

  11. Khurana R, Agarwal A, Bajpai VK, et al. Unraveling the amyloid associated with human medullary thyroid carcinoma. Endocrinology 145(12):5465–5470, 2004.

    Article  CAS  PubMed  Google Scholar 

  12. Sipe JD, Benson MD, Buxbaum JN, Ikeda, S, Merlini G, Saraiva MJM, Westermark P. Nomenclature 2014: Amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid 21(4):221–224, 2014.

    Article  PubMed  Google Scholar 

  13. Knowles TPJ, Vendruscolo M, Dobson CM. The amyloid state and its association with protein misfolding diseases. Nat Rev Mol Cell Biol 15:384–396, 2014.

    Article  CAS  PubMed  Google Scholar 

  14. Chiti F and Dobson CM. Protein misfolding, functional amyloid, and human disease. Annu Rev Bioch 75:333–366, 2006.

    Article  CAS  Google Scholar 

  15. Benedum UM, Lamouroux A, Konecki DS, et al. The Primary structure of human secretogranin I (chromogranin B): comparison with chromogranin A reveals homologous terminal domains and a large intervening variable region. EMBO J 6(5): 1203–1211, 1987.

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Durham P and Russo A. Stimulation of the calcitonin gene-related peptide enhancer by mitogen-activated protein kinases and repression by an antimigraine drug in trigeminal ganglia neurons. J Neurosci 23(3):807–815, 2003

    CAS  PubMed  Google Scholar 

  17. Schafers M, Svensson CI, Sommer C, Sorkin LS. Tumor necrosis factor-alpha induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons. J Neurosci 23(7):2517–2521, 2003.

    CAS  PubMed  Google Scholar 

  18. Arulmani U, VanDenBrink AM, Villalon CM, Saxena PR. Calcitonin gene-related peptide and its role in migraine pathophysiology. Eur J Pharmacol 500(1–3):315–330, 2004.

    Article  CAS  PubMed  Google Scholar 

  19. Russell FA, King R, Smillie SJ, et al. Calcitonin gene-related peptide: physiology and pathophysiology. Brain Physiological Reviews 94(4):1099–1142, 2014.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55901, USA

    Lori A. Erickson, Julie A. Vrana, Jason Theis, Michael Rivera, Ricardo V. Lloyd, Ellen McPhail & Jun Zhang

Authors
  1. Lori A. Erickson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julie A. Vrana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jason Theis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Rivera
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ricardo V. Lloyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ellen McPhail
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lori A. Erickson.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erickson, L.A., Vrana, J.A., Theis, J. et al. Analysis of Amyloid in Medullary Thyroid Carcinoma by Mass Spectrometry-Based Proteomic Analysis. Endocr Pathol 26, 291–295 (2015). https://doi.org/10.1007/s12022-015-9390-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12022-015-9390-7

Keywords

Search

Navigation