title: Cleavage of E-Cadherin Contributes to Defective Barrier Function in Neosquamous Epithelium.
abstract: After ablation of Barrett's esophagus (BE), the esophagus heals with neosquamous epithelium (NSE). Despite normal endoscopic appearance, NSE exhibits defective barrier function with similarities to defects noted in the distal esophageal epithelium in patients with gastroesophageal reflux disease (GERD).
  
  
  
  To determine whether patients with NSE, unlike patients with healthy esophageal epithelium, have C-terminal fragments (CTFs) of e-cad detectable on tissue biopsy. Secondly, to determine whether patients with NSE have elevated levels of N-terminal fragments (NTFs) of e-cad in the serum.
  
  
  
  Fifteen patients with ablated long-segment BE, who had healing with formation of NSE, were enrolled in this pilot study. Western blots for CTFs and NTFs were performed on biopsies of NSE. Venous blood was obtained to assess levels of NTFs. Endoscopic distal esophageal biopsies from patients without esophageal disease served as tissue controls. Control blood samples were obtained from healthy subjects.
  
  
  
  Blots of NSE were successful in 14/15 patients, and all 14 (100 %) had a 35-kD CTF of e-cad, while CTFs were absent in healthy control tissues. Despite CTFs in NSE, serum NTFs of e-cad in NSE were similar to controls, p > 0.05. However, unlike healthy controls, blots of NSE also showed NTFs with molecular weights of 70-90 kD.
  
  
  
  Cleavage of e-cad, as evidenced by the presence of CTFs and NTFs on biopsy, contributes to defective barrier function in NSE. However, unlike findings reported in GERD patients, serum NTFs are not elevated in NSE patients. This difference may reflect poor absorption with tissue entrapment of NTFs in previously ablated areas with poorly perfused NSE.
authors.affiliation: Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, CB#7080, Chapel Hill, NC, 27599-7080, USA. thomas.runge@unchealth.unc.edu.
authors.forename: Thomas M
authors.identifier: 0000-0003-3000-7580
authors.initials: TM
authors.lastname: Runge
authors.affiliation: Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, CB#7080, Chapel Hill, NC, 27599-7080, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.affiliation: Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, CB#7080, Chapel Hill, NC, 27599-7080, USA.
authors.forename: Zorka
authors.initials: Z
authors.lastname: Djukic
authors.affiliation: Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, CB#7080, Chapel Hill, NC, 27599-7080, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hallquist
authors.affiliation: Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, CB#7080, Chapel Hill, NC, 27599-7080, USA.
authors.forename: Roy C
authors.initials: RC
authors.lastname: Orlando
mesh_terms: D000368:Aged; D001471:Barrett Esophagus / Q000601:surgery*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D016022:Case-Control Studies; D017115:Catheter Ablation; D015331:Cohort Studies; D000071041:Esophageal Mucosa / Q000378:metabolism* / Q000473:pathology; D004945:Esophagoscopy; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010539:Permeability; D010865:Pilot Projects; D011446:Prospective Studies; D014945:Wound Healing
chemical_list: D015820:Cadherins
keywords: Barrett’s esophagus; ELISA; Esophageal permeability; Radiofrequency ablation; Western blot