Immunohistochemical Expression of N-Cadherin, but Not Plakoglobin and Plakophilin, Is Decreased in Pathologically Diagnosed Autopsy-Based Cases of Arrhythmogenic Right Ventricular Cardiomyopathy
F Tavora, M Franco, WS Chu, N Cresswell, A Burke. Paulista Medical School, Federal University of Sao Paulo, Sao Paulo, SP, Brazil; Armed Forces Institute of Pathology, Washington, DC; University of Maryland, Baltimore, MD
Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder related to mutations in desmosomal proteins. There have been few histologic studies quantitating expression of desmosomal proteins in autopsy samples of AC.
Design: We studied 29 patients (20 males, 9 females) dying suddenly with ARVC. Their age at death was 33 ± 4 and 32 ± 6 years, respectively. Control subject tissues were 15 men and 7 women, mean ages 36 ± 4 and 32 ± 6 years, respectively. Sections of heart were taken from short axis cuts: 25 sections from control tissues (10 right ventricle-RV, 12 left ventricular free wall-LV, and 3 ventricular septum-VS) and 58 sections from AC (26 RV, 23 LV, and 9 VS). Areas free of fibrofatty change were assessed. Immunohistochemical stains against plakoglobin, plakophilin, and N-cadherin were applied and area expression analyzed by both computerized morphometry correlated with a three-point scale of staining intensity and semi-quantitatevely independently by two pathologists.
Results: The mean area of plakoglobin (5.7%) and plakophilin (5.4%) showed no difference by gender, cardiac site (left ventricle, right ventricle and ventricular septum), patient age, or presence of ARVC. The mean area of N-cadherin staining showed no difference by gender (5.1 ± 0.5% in men vs. 5.1 ± 0.3% in women, p=.99), age (p=.08), or cardiac site (p = 0.7). The mean % staining of N-cadhrein by morphometry was 6.7 ± 0.4% in controls (range 2-14%, vs. 4.5 ± 0.3% in ARVC (ragne 1-14%), p=.0009. A positive predictive value of weak (1+ staining) for ARVC was 76%, with a negative predictive value of 50% (88% sensitivity, and 30% specificity, respectively). By multivariate analysis, % N-cadherin staining was inversely proportional with the presence of ARVC, independent of other variables (p=.0001).
Conclusions: We conclude that immunohistochemical evaluation of plakophilin and plakoglobin does not distinguish ARVC from controls. The relationship between specific mutations in cases of pathologically proven AC and the expression of desmosomal-related proteins needs to be further evaluated. N-cadherin is significantly decreased, but as a qualitative measure is not a specific diagnostic tool.
Monday, March 22, 2010 11:00 AM
Platform Session: Section G 2, Monday Morning