Tavora Fabio, Zhang Mingchang, Cresswell Nathaniel, Li Ling, Fowler David, Franco Marcello, Burke Allen
Escola Paulista de Medicina/UNIFESP, Sao Paulo, Brazil.
Open Cardiovasc Med J. 2013 Mar 29;7:28-35. doi: 10.2174/1874192401307010028. Print 2013.
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.
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.
The small and insignificant decrease in junction protein expression in ARVC suggests that immunohistochemistry is not a useful tool for the diagnosis.
致心律失常性右室心肌病（ARVC）是一种与桥粒蛋白突变相关的遗传性疾病。本研究通过研究经尸检确诊的ARVC病例，检验桥粒蛋白免疫组化染色具有诊断效用这一假设。
我们研究了23例因ARVC猝死患者的心脏。对照组织为21例因非心脏原因死亡者（n = 15）、扩张型心肌病患者（n = 3）和冠状动脉疾病患者（n = 3）的心脏。对ARVC组50个切片（24个左心室，26个右心室）和对照组28个切片中无纤维脂肪变性或瘢痕形成的区域进行评估。应用针对桥粒斑珠蛋白、桥粒芯蛋白、桥粒斑蛋白、连接蛋白43和N-钙黏蛋白的免疫组化染色，并通过计算机形态测量法分析区域表达。将结蛋白染色作为固定对照并进行类似分析。对照组和ARVC组结蛋白表达的平均面积相似（86%对85%，p = 0.6）。对照组桥粒斑珠蛋白表达为4.9%±0.3%，ARVC组为4.6%±0.3%（p = 0.3）。对照组桥粒芯蛋白染色为4.8%±0.3%，ARVC组为4.4%±0.3%（p = 0.3）。对照组桥粒斑蛋白染色为3.4%，ARVC组为3.2%±0.2%（p = 0.6）。左右心室染色比较时无显著差异（所有p>0.1）。对于非桥粒蛋白，连接蛋白43染色的平均面积在患病与否之间无显著差异。
ARVC中连接蛋白表达的微小且无显著意义的降低表明免疫组化不是一种有用的诊断工具。
