TY - JOUR
T1 - Usefulness of immunostaining for plakoglobin as a diagnostic marker of arrhythmogenic right ventricular cardiomyopathy
AU - Munkholm, Julie
AU - Christensen, Alex H
AU - Svendsen, Jesper H
AU - Andersen, Claus B
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/1/15
Y1 - 2012/1/15
N2 - The clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging due to phenotypic variation, reduced/age-related penetrance, and lack of a diagnostic test. A single report has suggested quantitative myocardial immunoanalysis for the desmosomal protein plakoglobin as a diagnostic test with high sensitivity and specificity. We performed immunohistochemistry for plakoglobin and a control protein on myocardial biopsies with fibrofatty replacements from 50 consecutive, unrelated patients. The clinical, genetic, and immunohistochemical data were evaluated by independent observers in a blinded manner. The immunohistochemical and clinical diagnoses were compared and the sensitivity, specificity, and predictive values calculated. Our analysis showed 37 samples (74%) with a reduced immunosignal for plakoglobin. Of the 34 patients with a clinical diagnosis of ARVC, 29 displayed a reduced plakoglobin signal. Of the 14 patients with a clinical diagnosis other than ARVC, 6 displayed a reduced signal. Two patients were excluded from further analysis. A sensitivity of 85%, a specificity of 57%, a positive predictive value of 83%, and a negative predictive value of 62% were found. In conclusion, immunohistochemical analysis for plakoglobin, applied as a diagnostic test for ARVC, seems associated with a relatively high sensitivity, but limited specificity, and although additional validation is required, we advocate caution in basing clinical decision-making on the proposed diagnostic test.
AB - The clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging due to phenotypic variation, reduced/age-related penetrance, and lack of a diagnostic test. A single report has suggested quantitative myocardial immunoanalysis for the desmosomal protein plakoglobin as a diagnostic test with high sensitivity and specificity. We performed immunohistochemistry for plakoglobin and a control protein on myocardial biopsies with fibrofatty replacements from 50 consecutive, unrelated patients. The clinical, genetic, and immunohistochemical data were evaluated by independent observers in a blinded manner. The immunohistochemical and clinical diagnoses were compared and the sensitivity, specificity, and predictive values calculated. Our analysis showed 37 samples (74%) with a reduced immunosignal for plakoglobin. Of the 34 patients with a clinical diagnosis of ARVC, 29 displayed a reduced plakoglobin signal. Of the 14 patients with a clinical diagnosis other than ARVC, 6 displayed a reduced signal. Two patients were excluded from further analysis. A sensitivity of 85%, a specificity of 57%, a positive predictive value of 83%, and a negative predictive value of 62% were found. In conclusion, immunohistochemical analysis for plakoglobin, applied as a diagnostic test for ARVC, seems associated with a relatively high sensitivity, but limited specificity, and although additional validation is required, we advocate caution in basing clinical decision-making on the proposed diagnostic test.
KW - Adult
KW - Arrhythmogenic Right Ventricular Dysplasia
KW - Biopsy
KW - Diagnosis, Differential
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Middle Aged
KW - Myocardium
KW - Phenotype
KW - Retrospective Studies
KW - Severity of Illness Index
KW - Young Adult
KW - gamma Catenin
U2 - 10.1016/j.amjcard.2011.08.044
DO - 10.1016/j.amjcard.2011.08.044
M3 - Journal article
C2 - 22036107
SN - 0735-1097
VL - 109
SP - 272
EP - 275
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 2
ER -