E-cadherin but not β-catenin expression is decreased in laryngeal biopsies from patients with laryngopharyngeal reflux

Abstract

Abnormal exposure of acid refluxate on the esophageal mucosa has been shown to decrease the epithelial barrier function through an alteration in the intercellular junctional complex. However, only few studies have examined the molecular effects caused by abnormal exposure of gastric refluxate on the laryngeal epithelium. E-cadherin and beta-catenin are cell membrane-associated proteins playing a major role in the maintenance of cell-cell adhesion in epithelial tissues. In this study we tried to analyse the molecular effect of laryngopharyngeal reflux (LPR) on the cellular expression of these proteins. Therefore, we compared the expression of E-caherin and beta-catenin in laryngeal biopsies from patients with and without pH-documented laryngopharyngeal reflux. Paraffin-embedded archival laryngeal biopsies taken from 21 patients, who had undergone rigid laryngoscopy under general anaesthesia and postoperative 24-h pH monitoring, were evaluated immunohistochemically with antibodies to E-cadherin and beta-catenin. The membrane expression of the two proteins was categorized in no expression, mild, moderate and strong (grade 0-3). In LPR patients (n=14) the mean grade of E-cadherin and beta-catenin expression was 1.57 and 1.21, while in specimens of patients without pH-documented LPR it was 2.57 and 1.29. The difference in E-cadherin expression was statistically significant (P=0.011). From our findings we conclude that LPR can cause a decrease in the laryngeal expression of E-cadherin but not of beta-catenin. The reduction of E-cadherin-mediated adhesion could contribute to the development of laryngeal neoplasms. E-cadherin immunostaining of laryngeal biopsies could be a further diagnostic tool to confirm the diagnosis in patients with suspected LPR.

Association between laryngopharyngeal reflux and benign vocal folds lesions: A systematic review.

“…Thirty‐four publications were identified, and seven met our criteria (Table ) . The impact of LPR on the mucosa of the vocal folds has mainly been studied throughout the study of pepsin.…”

Raised intensity phonation compromises vocal fold epithelial barrier integrity

“…Thirty-minutes of mechanical stress reduced β–catenin but not E-cadherin mRNA expression. Immunohistochemistry of biopsy samples of patients with laryngopharyngeal reflux (LPR) demonstrate reduced E-cadherin but not β–catenin expression as compared to patients without LPR 15. The differential effects of LPR versus mechanical stress on reducing β–catenin expression are unclear but could be related to the localization of these proteins in vocal fold epithelium.…”

Vocal Fold Epithelial Barrier in Health and Injury: A Research Review

“…Laryngeal biopsy specimens from three laryngeal sites (vocal fold, posterior commissure, and ventricle) from patients with LPR were utilized to investigate the effects of this disease on the adherens junction protein, E-cadherin. At all tested sites, there was a significant decrease in E-cadherin expression (Gill et al, 2005; Johnston et al, 2003; Reichel, Mayr, Durst, & Berghaus, 2008). Franchi and colleagues (2007) observed further evidence of structural compromise in laryngeal epithelial biopsy specimens from the posterior commissure in patients with LPR.…”