TY  - JOUR
TI  - The complementary role of histology and proteomics for diagnosis and typing of systemic amyloidosis
AV  - public
Y1  - 2019/07//
EP  - 153
N2  - 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.
ID  - discovery10068066
KW  - Amyloid
KW  -  Immunohistochemistry
KW  -  Mass Spectrometry
KW  -  Proteomics
SP  - 145
VL  - 5
IS  - 3
N1  - 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.
UR  - https://doi.org/10.1002/cjp2.126
SN  - 2056-4538
JF  - Journal of Pathology: Clinical Research
A1  - Rezk, T
A1  - Gilbertson, JA
A1  - Mangione, PP
A1  - Rowczenio, D
A1  - Rendell, N
A1  - Canetti, D
A1  - Lachmann, HJ
A1  - Wechalekar, AD
A1  - Bass, P
A1  - Hawkins, PN
A1  - Bellotti, V
A1  - Taylor, GW
A1  - Gillmore, JD
ER  -