Classification of amyloidosis by laser microdissection and mass spectrometry–based proteomic analysis in clinical biopsy specimens
Open accessAbstract
The clinical management of amyloidosis is based on the treatment of the underlying etiology, and accurate identification of the protein causing the amyloidosis is of paramount importance. Current methods used for typing of amyloidosis such as immunohistochemistry have low specificity and sensitivity. In this study, we report the development of a highly specific and sensitive novel test for the typing of amyloidosis in routine clinical biopsy specimens. Our approach combines specific sampling by laser microdissection (LMD) and analytical power of tandem mass spectrometry (MS)–based proteomic analysis. We studied 50 cases of amyloidosis that were well-characterized by gold standard clinicopathologic criteria (training set) and an independent validation set comprising 41 cases of cardiac amyloidosis. By use of LMD/MS, we identified the amyloid type with 100% specificity and sensitivity in the training set and with 98% in validation set. Use of the LMD/MS method will enhance our ability to type amyloidosis accurately in clinical biopsy specimens.
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The second renal biopsy showed similar LM and IF findings to the first biopsy, but the density of deposits on EM were more obvious.
“Although the histological findings by LM and IF were similar to those of the first biopsy, the density of deposits on EM were more obvious, and ApoE was identified by immunohistochemical studies for LM and EM specimens using anti-ApoE antibody (Novus Biologicals, Littleton, CO, USA) (Fig. 3) [8].”
From Membranous Nephropathy-Like Apolipoprotein E Deposition Disease with Apolipoprotein E Toyonaka (Ser197Cys) and a Homozygous Apolipoprotein E2/2 (2018) · cites this paper as [8]
The Clinical specimens and Results and discussion sections describe amyloidosis biopsy samples and mass-spectrometry findings, but no comparison of a first and second renal biopsy by LM, IF, or EM. Searches for those biopsy comparisons and deposit density found no supporting passage in our copy. (LLM, conf=0.76)
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- Authors
- Vrana, J. A., Gamez, J. D., Madden, B. J., Theis, J. D., Bergen, H. R., & Dogan, A.
- Affiliations
- Department of Laboratory Medicine and Pathology, and
- Mayo Clinic (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-12-03
- Volume
- 114
- Issue
- 24
- Pages
- 4957-4959
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2046882226
- Cited by
- 904
- References
- 0
- Citations by year
- 2026: 35 · 2025: 48 · 2024: 44 · 2023: 54 · 2022: 50 · 2021: 61 · 2020: 72 · 2019: 56 · 2018: 57 · 2017: 63 · 2016: 68 · 2015: 62 · 2014: 55 · 2013: 60 · 2012: 60
- FWCI
- 15.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- amyloidosis, amyloid typing, laser microdissection, tandem mass spectrometry, proteomics, cardiac amyloidosis, biopsy specimens
- MeSH terms
- Amyloidosis, Female, Humans, Lasers, Male, Sensitivity and Specificity, Proteomics, Microdissection, Tandem Mass Spectrometry
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