Quantitative Immunohistochemistry of Desmosomal Proteins (Plakoglobin, Desmoplakin and Plakophilin), Connexin-43, and N-cadherin in Arrhythmogenic Cardiomyopathy: An Autopsy Study



Fabio Tavora1, *, Mingchang Zhang 3, 4, Nathaniel Cresswell 2, Ling Li 1, 4, 5, David Fowler5, Marcello Franco 1, Allen Burke 5
1 Escola Paulista de Medicina/UNIFESP, Sao Paulo, Brazil
2 Georgetown University, Washington, D.C., USA
3 The Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China
4 Division of Forensic Medicine, Key Laboratory of Evidence Sciences, China University of Political Science and Law, Beijing, China
5 University of Maryland Medical Center, Baltimore, USA


Article Metrics

CrossRef Citations:
6
Total Statistics:

Full-Text HTML Views: 721
Abstract HTML Views: 438
PDF Downloads: 128
Total Views/Downloads: 1287
Unique Statistics:

Full-Text HTML Views: 269
Abstract HTML Views: 178
PDF Downloads: 87
Total Views/Downloads: 534



© Tavora et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Escola Paulista de Medicina/UNIFESP, Sao Paulo, Brazil; Tel: +558532658393; Fax: +558532658394; E-mail: fabio.tavora@argospatologia.com.br


Abstract

Background:

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder related to mutations in desmosomal proteins. The current study tests the hypothesis that immunohistochemical staining for desmosomal proteins is of diagnostic utility by studying autopsy-confirmed cases of ARVC.

Methods and Results:

We studied 23 hearts from patients dying suddenly with ARVC. Control subject tissues were 21 hearts from people dying from non-cardiac causes (n=15), dilated cardiomyopathy (n=3) and coronary artery disease (n=3).

Areas free of fibrofatty change or scarring were assessed on 50 sections from ARVC (24 left ventricle, 26 right ventricle) and 28 sections from controls. Immunohistochemical stains against plakoglobin, plakophilin, desmoplakin, connexin-43, and N-cadherin were applied and area expression analyzed by computerized morphometry. Desmin was stained as a control for fixation and similarly analyzed.

The mean area of desmin expression was similar in controls and ARVC (86% vs. 85%, p=0.6). Plakoglobin expression was 4.9% ± 0.3% in controls, vs. 4.6% ± 0.3% in ARVC (p=0.3). Plakophilin staining was 4.8% ± 0.3% in controls vs. 4.4% ± 03% in ARVC (p=0.3). Desmoplakin staining was 3.4% in controls vs. 3.2 ± 0.2% in ARVC (p=0.6). There were no significant differences when staining was compared between right and left ventricles (all p > 0.1).

For non-desmosomal proteins, the mean area of connexin-43 staining showed no significant difference by presence of disease.

Conclusions:

The small and insignificant decrease in junction protein expression in ARVC suggests that immunohistochemistry is not a useful tool for the diagnosis.

Keywords: ARVC, arrhytmogenic cardiomyopaty, sudden death, autopsy..