Usefulness of immunostaining for plakoglobin as a diagnostic marker of arrhythmogenic right ventricular cardiomyopathy.
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.
Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Denmark. munkholm@dadlnet.dk
Julie
J
Munkholm
Alex H
AH
Christensen
Jesper H
JH
Svendsen
Claus B
CB
Andersen
D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult; D051185:gamma Catenin / Q000378:metabolism*
D051185:gamma Catenin