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Implementation and evaluation of amyloidosis subtyping by laser-capture microdissection and tandem mass spectrometry.
- Source :
- Clinical Proteomics; 10/27/2016, Vol. 13, p1-6, 6p
- Publication Year :
- 2016
-
Abstract
- Background: Correct identification of the amyloidosis-causing protein is crucial for clinical management. Recently the Mayo Clinic reported laser-capture microdissection (LCM) with liquid chromatography-coupled tandem mass spectrometry (MS/MS) as a new diagnostic tool for amyloid diagnosis. Here, we report an independent implementation of this proteomic diagnostics method at the Princess Alexandra Hospital Amyloidosis Centre in Brisbane, Australia. Results: From 2010 to 2014, 138 biopsies received from 35 different organ sites were analysed by LCM-MS/MS using Congo Red staining to visualise amyloid deposits. There was insufficient tissue in the block for LCM for 7 cases. An amyloid forming protein was ultimately identified in 121 out of 131 attempted cases (94 %). Of the 121 successful cases, the Mayo Clinic amyloid proteomic signature (at least two of Serum Amyloid P, ApoE and ApoA4) was detected in 92 (76 %). Low levels of additional amyloid forming proteins were frequently identified with the main amyloid forming protein, which may reflect co-deposition of fibrils. Furthermore, vitronectin and clusterin were frequently identified in our samples. Adding vitronectin to the amyloid signature increases the number of positive cases, suggesting a potential 4th protein for the signature. In terms of clinical impact, amyloid typing by immunohistochemistry was attempted in 88 cases, reported as diagnostic in 39, however, 5 were subsequently revealed by proteomic analysis to be incorrect. Overall, the referring clinician's diagnosis of amyloid subtype was altered by proteomic analysis in 24 % of cases. While LCM-MS/MS was highly robust in protein identification, clinical information was still required for subtyping, particularly for systemic versus localized amyloidosis. Conclusions: This study reports the independent implementation and evaluation of a proteomics-based diagnostic for amyloidosis subtyping. Our results support LCM-MS/MS as a powerful new diagnostic technique for amyloidosis, but also identified some challenges and further development opportunities. [ABSTRACT FROM AUTHOR]
- Subjects :
- AMYLOIDOSIS
LASER surgery
MICRODISSECTION
TANDEM mass spectrometry
PROTEOMICS
Subjects
Details
- Language :
- English
- ISSN :
- 15426416
- Volume :
- 13
- Database :
- Complementary Index
- Journal :
- Clinical Proteomics
- Publication Type :
- Academic Journal
- Accession number :
- 119301606
- Full Text :
- https://doi.org/10.1186/s12014-016-9133-x