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The complementary role of histology and proteomics for diagnosis and typing of systemic amyloidosis

Rezk, T; Gilbertson, JA; Mangione, PP; Rowczenio, D; Rendell, N; Canetti, D; Lachmann, HJ; ... Gillmore, JD; + view all (2019) The complementary role of histology and proteomics for diagnosis and typing of systemic amyloidosis. Journal of Pathology: Clinical Research , 5 (3) pp. 145-153. 10.1002/cjp2.126. Green open access

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Abstract

The tissue diagnosis of amyloidosis and confirmation of fibril protein type, which are crucial for clinical management, have traditionally relied on Congo red (CR) staining followed by immunohistochemistry (IHC) using fibril protein specific antibodies. However, amyloid IHC is qualitative, non-standardised, requires operator expertise, and not infrequently fails to produce definitive results. More recently, laser dissection mass spectrometry (LDMS) has been developed as an alternative method to characterise amyloid in tissue sections. We sought to compare these techniques in a real world setting. During 2017, we performed LDMS on 640 formalin-fixed biopsies containing amyloid (CR+ve) comprising all 320 cases that could not be typed by IHC (IHC-ve) and 320 randomly selected CR+ve samples that had been typed (IHC+ve). In addition, we studied 60 biopsies from patients in whom there was a strong suspicion of amyloidosis, but in whom histology was non-diagnostic (CR-ve). Comprehensive clinical assessments were conducted in 532 (76%) of cases. Among the 640 CR+ve samples, 602 (94%) contained ≥ 2 of 3 amyloid signature proteins (ASPs) on LDMS (ASP+ve) supporting the presence of amyloid. 49 of the 60 CR-ve samples were ASP-ve; 7/11 that were ASP+ve were glomerular. The amyloid fibril protein was identified by LDMS in 255/320 (80%) of the IHC-ve samples and in a total of 545/640 (85%) cases overall. The LDMS and IHC techniques yielded discordant results in only 7/320 (2%) cases. CR histology and LDMS are corroborative for diagnosis of amyloid, but LDMS is superior to IHC for confirming amyloid type. This article is protected by copyright. All rights reserved.

Type: Article
Title: The complementary role of histology and proteomics for diagnosis and typing of systemic amyloidosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cjp2.126
Publisher version: https://doi.org/10.1002/cjp2.126
Language: English
Additional information: Copyright © 2019 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Keywords: Amyloid, Immunohistochemistry, Mass Spectrometry, Proteomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10068066
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