Abstract
The developments in mass spectrometry-based proteomic technologies have created unprecedented opportunities for identification of proteins in routine clinical biopsy specimens. The application of the technology to classification of amyloidosis has resulted in the first clinical application of shotgun proteomics. In the context of amyloid classification, mass spectrometry-based proteomic assays offer many advantages over immunoassay-based methods and clinical surrogates. The method is readily applicable to FFPE or fresh/frozen routine clinical biopsy specimens and requires very little tissue. Unlike immunoassays which require good reagents for each target, LC–MS/MS can detect all amyloidogenic proteins in a single analysis. Given these analytical and operational advantages, and the far superior specificity and sensitivity offered by laser microdissection (LMD) and LC–MS/MS based methods, LMD- and LC–MS/MS-based analysis is now considered the gold standard for classification of amyloidosis.
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References
Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJ, Westermark P. Nomenclature 2014: amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid. 2014;21:221–4.
Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583–96.
Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol. 2011;29:1924–33.
Holmgren G, Ericzon BG, Groth CG, et al. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet. 1993;341:1113–6.
Stangou AJ, Hawkins PN. Liver transplantation in transthyretin-related familial amyloid polyneuropathy. Curr Opin Neurol. 2004;17:615–20.
Howie AJ, Brewer DB, Howell D, Jones AP. Physical basis of colors seen in Congo red-stained amyloid in polarized light. Lab Invest. 2008;88:232–42.
Picken MM, Herrera GA. The burden of “sticky” amyloid: typing challenges. Arch Pathol Lab Med. 2007;131:850–1.
Solomon A, Murphy CL, Westermark P. Unreliability of immunohistochemistry for typing amyloid deposits. Arch Pathol Lab Med. 2008;132:14–5.
Picken MM. New insights into systemic amyloidosis: the importance of diagnosis of specific type. Curr Opin Nephrol Hypertens. 2007;16:196–203.
Murphy CL, Eulitz M, Hrncic R, et al. Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens. Am J Clin Pathol. 2001;116:135–42.
Murphy CL, Wang S, Williams T, Weiss DT, Solomon A. Characterization of systemic amyloid deposits by mass spectrometry. Methods Enzymol. 2006;412:48–62.
Kaplan B, Martin BM, Livneh A, Pras M, Gallo GR. Biochemical subtyping of amyloid in formalin-fixed tissue samples confirms and supplements immunohistologic data. Am J Clin Pathol. 2004;121:794–800.
Rodriguez FJ, Gamez JD, Vrana JA, et al. Immunoglobulin derived depositions in the nervous system: novel mass spectrometry application for protein characterization in formalin-fixed tissues. Lab Invest. 2008;88:1024–37.
Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen 3rd HR, Dogan A. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009;114:4957–9.
Hood BL, Darfler MM, Guiel TG, et al. Proteomic analysis of formalin-fixed prostate cancer tissue. Mol Cell Proteomics. 2005;4:1741–53.
Prieto DA, Hood BL, Darfler MM, et al. Liquid tissue: proteomic profiling of formalin-fixed tissues. Biotechniques. 2005;38(Suppl):32–5.
Palmer-Toy DE, Krastins B, Sarracino DA, Nadol Jr JB, Merchant SN. Efficient method for the proteomic analysis of fixed and embedded tissues. J Proteome Res. 2005;4:2404–11.
Guo T, Wang W, Rudnick PA, et al. Proteome analysis of microdissected formalin-fixed and paraffin-embedded tissue specimens. J Histochem Cytochem. 2007;55:763–72.
Dasari S, Theis JD, Vrana JA, et al. Clinical proteome informatics workbench detects pathogenic mutations in hereditary amyloidosis. J Proteome Res. 2014;13:2352–8.
Brambilla F, Lavatelli F, Di Silvestre D, et al. Reliable typing of systemic amyloidosis through proteomic analysis of subcutaneous adipose tissue. Blood. 2012;119:1844–7.
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. 2014;99:1239–47.
Sethi S, Theis JD, Leung N, et al. Mass spectrometry-based proteomic diagnosis of renal immunoglobulin heavy chain amyloidosis. Clin J Am Soc Nephrol. 2010;5:2180–7.
Dogan A, Theis JD, Vrana JA, et al. Clinical and pathological phenotype of leukocyte cell-derived chemotaxin-2 (LECT2) amyloidosis (ALECT2). Amyloid. 2010;17:69–70.
Klein CJ, Vrana JA, Theis JD, et al. Mass spectrometric-based proteomic analysis of amyloid neuropathy type in nerve tissue. Arch Neurol-Chicago. 2011;68:195–9.
Miller DV, Dogan A, Sethi S. New-onset proteinuria with massive amorphous glomerular deposits. Am J Kidney Dis. 2010;55:749–54.
Lacy MQ, Theis JD, Vrana JA, et al. Lysozyme amyloidosis (ALys) affecting a family with a new variant of lysozyme gene (LYZ) and hereditary haemorrhagic telangiectasia. Amyloid. 2010;17:125.
Rowczenio D, Dogan A, Theis JD, et al. Amyloidogenicity and clinical phenotype associated with five novel mutations in Apolipoprotein A-I. Am J Pathol. 2011;179:1978–87.
D’Souza A, Theis JD, Vrana JA, Dogan A. Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration. Amyloid. 2014;21:71–5.
Valleix S, Gillmore JD, Bridoux F, et al. Hereditary systemic amyloidosis due to Asp76Asn variant beta2-microglobulin. N Engl J Med. 2012;366:2276–83.
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Dogan, A. (2015). Classification of Amyloidosis by Mass Spectrometry-Based Proteomics. In: Picken, M., Herrera, G., Dogan, A. (eds) Amyloid and Related Disorders. Current Clinical Pathology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-19294-9_23
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DOI: https://doi.org/10.1007/978-3-319-19294-9_23
Publisher Name: Humana Press, Cham
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