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Mass spectrometry-based absolute quantification of amyloid proteins in pathology tissue specimens: Merits and limitations.


ABSTRACT: To clarify the significance of quantitative analyses of amyloid proteins in clinical practice and in research relating to systemic amyloidoses, we applied mass spectrometry-based quantification by isotope-labeled cell-free products (MS-QBIC) to formalin-fixed, paraffin-embedded (FFPE) tissues. The technique was applied to amyloid tissues collected by laser microdissection of Congo red-stained lesions of FFPE specimens. Twelve of 13 amyloid precursor proteins were successfully quantified, including serum amyloid A (SAA), transthyretin (TTR), immunoglobulin kappa light chain (IGK), immunoglobulin lambda light chain (IGL), beta-2-microglobulin (B2M), apolipoprotein (Apo) A1, Apo A4, Apo E, lysozyme, Apo A2, gelsolin, and fibrinogen alpha chain; leukocyte cell-derived chemotaxin-2 was not detected. The quantification of SAA, TTR, IGK, IGL, and B2M confirmed the responsible proteins, even when the immunohistochemical results were not decisive. Considerable amounts of Apo A1, Apo A4, and Apo E were deposited in parallel amounts with the responsible proteins. Quantification of amyloid protein by MS-QBIC is feasible and useful for the classification of and research on systemic amyloidoses.

SUBMITTER: Ogawa M 

PROVIDER: S-EPMC7329117 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Mass spectrometry-based absolute quantification of amyloid proteins in pathology tissue specimens: Merits and limitations.

Ogawa Makiko M   Shintani-Domoto Yukako Y   Nagashima Yoshiki Y   Ode Koji L KL   Sato Aya A   Shimizu Yoshihiro Y   Ohashi Kenichi K   Roehrl Michael H A MHA   Ushiku Tetsuo T   Ueda Hiroki R HR   Fukayama Masashi M  

PloS one 20200701 7


To clarify the significance of quantitative analyses of amyloid proteins in clinical practice and in research relating to systemic amyloidoses, we applied mass spectrometry-based quantification by isotope-labeled cell-free products (MS-QBIC) to formalin-fixed, paraffin-embedded (FFPE) tissues. The technique was applied to amyloid tissues collected by laser microdissection of Congo red-stained lesions of FFPE specimens. Twelve of 13 amyloid precursor proteins were successfully quantified, includi  ...[more]

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