Background: Juvenile sudden cardiac death (SCD) can be due to a variety of acquired and inherited conditions, and is often the first manifestation of a hidden genetic disease. Arrhythmogenic right ventricular cardiomyopathy (ARVC) due to mutations in desmosomal proteins is one of the most frequent causes of SCD. Autopsy diagnosis of ARVC is based on the findings of myocardial atrophy and fatty/fibro-fatty replacement. However, cases with mild and segmental fibro-fatty replacement still represent a diagnostic grey zone between desmosomal-related ARVC and non-specific myocardial changes. Immunohistochemical (IH) detection of plakoglobin (PKG), a protein of intercalated disks, has been recently proposed as a diagnostic tool for histologic diagnosis of ARVC. We studied the usefulness of this method to rule out ARVC in cases of juvenile SCD with morphologic features suggestive but not conclusive for the disease. Methods: We selected 4 cases with autopsy features suggestive of ARVC in which a clinical family screening, along with a molecular autopsy of the proband had allowed a post-mortem diagnosis of channelopathy (CPVT, figure 1; LQTS, figure 2; Brugada syndrome, figure 3 and 4). As positive controls, we used 3 explanted hearts with clinically and genetically proven ARVC (Table 1). IH was performed on paraffin slides from both ventricles, with antibodies to PKG and N-Cadherin as internal control, using immunoperoxidase with conventional labeled polymer technology, with a 1: 50.000 antibody dilution. Results: Plakoglobin was intensely expressed at myocyte intercalated disks, both in the right and left ventricles, in all cases of channelopathies with morphologic changes suggestive of ARVC. In contrast, it was markedly reduced or absent in explanted ARVC hearts, confirming the clinical and morphologic findings. According to our preliminary results, in cases of SCD with ambiguous morphologic features, diffuse positive stain of intercalated disks is useful to rule out the diagnosis of desmosomal-related ARVC. PKG immunohistochemistry can be an additional tool for autopsy diagnosis, that is crucial to guide the genetic screening of SCD, expecially in absence of a significant clinical history or previous instrumental findings.
Role of Plakoglobin Immunohistochemistry in Diagnostic Evaluation of Juvenile Sudden Cardiac Death / Giordano, Carla; Orlandi, Maurizia; Mariangela, Sebastiani; P. F., Silenzi; DI GIOIA, Cira Rosaria Tiziana; Crt Di, Gioia; F., Musumeci; E., Zachara; P. L., Della Monica; Gallo, Pietro; D'Amati, Giulia. - In: LABORATORY INVESTIGATION. - ISSN 0023-6837. - STAMPA. - 90:1(2010), pp. 81A-82A. (Intervento presentato al convegno 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology tenutosi a Washington, DC nel MAR 20-26, 2010).
Role of Plakoglobin Immunohistochemistry in Diagnostic Evaluation of Juvenile Sudden Cardiac Death
GIORDANO, Carla;ORLANDI, MAURIZIA;DI GIOIA, Cira Rosaria Tiziana;GALLO, Pietro;D'AMATI, Giulia
2010
Abstract
Background: Juvenile sudden cardiac death (SCD) can be due to a variety of acquired and inherited conditions, and is often the first manifestation of a hidden genetic disease. Arrhythmogenic right ventricular cardiomyopathy (ARVC) due to mutations in desmosomal proteins is one of the most frequent causes of SCD. Autopsy diagnosis of ARVC is based on the findings of myocardial atrophy and fatty/fibro-fatty replacement. However, cases with mild and segmental fibro-fatty replacement still represent a diagnostic grey zone between desmosomal-related ARVC and non-specific myocardial changes. Immunohistochemical (IH) detection of plakoglobin (PKG), a protein of intercalated disks, has been recently proposed as a diagnostic tool for histologic diagnosis of ARVC. We studied the usefulness of this method to rule out ARVC in cases of juvenile SCD with morphologic features suggestive but not conclusive for the disease. Methods: We selected 4 cases with autopsy features suggestive of ARVC in which a clinical family screening, along with a molecular autopsy of the proband had allowed a post-mortem diagnosis of channelopathy (CPVT, figure 1; LQTS, figure 2; Brugada syndrome, figure 3 and 4). As positive controls, we used 3 explanted hearts with clinically and genetically proven ARVC (Table 1). IH was performed on paraffin slides from both ventricles, with antibodies to PKG and N-Cadherin as internal control, using immunoperoxidase with conventional labeled polymer technology, with a 1: 50.000 antibody dilution. Results: Plakoglobin was intensely expressed at myocyte intercalated disks, both in the right and left ventricles, in all cases of channelopathies with morphologic changes suggestive of ARVC. In contrast, it was markedly reduced or absent in explanted ARVC hearts, confirming the clinical and morphologic findings. According to our preliminary results, in cases of SCD with ambiguous morphologic features, diffuse positive stain of intercalated disks is useful to rule out the diagnosis of desmosomal-related ARVC. PKG immunohistochemistry can be an additional tool for autopsy diagnosis, that is crucial to guide the genetic screening of SCD, expecially in absence of a significant clinical history or previous instrumental findings.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
