Phospholamban immunostaining is a highly sensitive and specific method for diagnosing phospholamban p.Arg14del cardiomyopathy
Publication date
2017-09
Authors
te Rijdt, Wouter P.
van der Klooster, Z Joy
Hoorntje, Edgar T
Jongbloed, Jan D. H.
van der Zwaag, Paul A.
Asselbergs, Folkert W
Dooijes, Dennis
de Boer, Rudolf A.
van Tintelen, J Peter
van den Berg, Maarten P.
Editors
Advisors
Supervisors
Document Type
Article
Metadata
Show full item recordCollections
License
Abstract
Phospholamban (PLN) p.Arg14del cardiomyopathy is associated with an increased risk of malignant ventricular arrhythmias and severe heart failure and a poor prognosis from late adolescence. It can be diagnosed in whole heart specimens, but rarely in right ventricular biopsy specimens, by PLN immunohistochemistry showing PLN-containing aggregates concentrated in cardiomyocytes in dense perinuclear aggresomes. The purpose of this study was to determine whether PLN immunohistochemistry can be used to diagnose PLN p.Arg14del cardiomyopathy using apical left ventricular myocardial specimens harvested during left ventricular assist device (LVAD) implantation. At that stage, a genetic diagnosis, which may guide treatment and referral of family members for further investigation, is frequently not established yet. Included were myocardial specimens from 30 diverse genetic cardiomyopathy cases with known variants (9 carriers of the pathogenic PLN p.Arg14del variant, 18 cases with other pathogenic or likely pathogenic variants in cardiomyopathy-related genes, and 3 with only variants of unknown significance). Immunohistochemical analysis revealed typical dense perinuclear globular PLN-positive aggregates, representing aggresomes, in all nine PLN p.Arg14del cases. In 20 non-PLN cases, PLN-staining was absent. In one non-PLN case, one of the two independent observers misinterpreted PLN staining of heavily wrinkled nuclear membranes of cardiomyocytes as perinuclear PLN aggregates. In this genetic cardiomyopathy cohort, PLN Immunohistochemical analysis in LVAD biopsies was found to be a highly sensitive (100%) and specific (95%) method for demonstration of PLN protein aggregates in PLN p.Arg14del cardiomyopathy. In clinical practice, PLN immunohistochemical analysis of LVAD specimens can be of incremental value in the diagnostic workup of this cardiomyopathy, even more so if genetic analysis is not readily available.
Keywords
Apical left ventricular assist device specimen, Genetic cardiomyopathy, Immunohistochemistry, Next-generation sequencing, Phospholamban, Protein aggregation, Journal Article
Citation
te Rijdt, W P, van der Klooster, Z J, Hoorntje, E T, Jongbloed, J D H, van der Zwaag, P A, Asselbergs, F W, Dooijes, D, de Boer, R A, van Tintelen, J P, van den Berg, M P, Vink, A & Suurmeijer, A J H 2017, 'Phospholamban immunostaining is a highly sensitive and specific method for diagnosing phospholamban p.Arg14del cardiomyopathy', Cardiovascular Pathology, vol. 30, pp. 23-26. https://doi.org/10.1016/j.carpath.2017.05.004