Laryngeal epithelial defenses against laryngopharyngeal reflux: investigations of E-cadherin, carbonic anhydrase isoenzyme III, and pepsin.

OBJECTIVES: This is the third annual report of an international research network studying the cellular impact of laryngopharyngeal reflux (LPR) on laryngeal epithelium. The objective of this study was to investigate the presence of E-cadherin (epithelial cadherin; the intercellular junctional complex protein) in relation to the presence of (intracellular) pepsin and carbonic anhydrase isoenzyme III (CAIII). METHODS: Fifty-four laryngeal biopsy specimens from 18 LPR patients were studied by immunohistochemistry and Western blotting for pepsin, E-cadherin, and CAIII. These data were compared to those from normal control subjects analyzed in another research study. RESULTS: Intracellular pepsin was detected in LPR patients, but not in controls. E-cadherin expression was reduced in patients with LPR. Carbonic anhydrase III expression was not found in the vocal fold or in the majority of samples taken from the ventricle of LPR patients and was inversely associated with E-cadherin membranous expression. CONCLUSIONS: The findings of depleted E-cadherin and CAIII and the presence of pepsin appear to correlate with LPR. The reduced protective response indicated by the reduced expression of CAIII may play an important role in the disruption of the intercellular barrier associated with the down-regulation of E-cadherin.

Cell biology of laryngeal epithelial defenses in health and disease: further studies.

This is the second annual report of an international collaborative research group that is examining the cellular impact of laryngopharyngeal reflux (LPR) on laryngeal epithelium. The results of clinical and experimental studies are presented. Carbonic anhydrase (CA), E-cadherin, and MUC gene expression were analyzed in patients with LPR, in controls, and in an in vitro model. In patients with LPR, we found decreased levels of CAIII in vocal fold epithelium and increased levels in posterior commissure epithelium. The experimental studies confirm that laryngeal CAIII is depleted in response to reflux. Also, cell damage does occur well above pH 4.0. In addition, E-cadherin (transmembrane cell surface molecules, which have a key function in epithelial cell adhesion) was not present in 37% of the LPR laryngeal specimens. In conclusion, the laryngeal epithelium lacks defenses comparable to those in esophageal epithelium, and these differences may contribute to the increased susceptibility of laryngeal epithelium to reflux-related injury.