Related Experiment Video
Updated: Oct 13, 2025
Diagnosis of Neoplasia in Barrett’s Esophagus using Vital-dye Enhanced Fluorescence Imaging
Published on: May 11, 2014
Agrin Loss in Barrett's Esophagus-Related Neoplasia and Its Utility as a Diagnostic and Predictive Biomarker
Steffen Rickelt1, Azfar Neyaz2, Charlene Condon1,3
1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Purpose:
There is an unmet need for identifying novel biomarkers in Barrett's esophagus that could stratify patients with regards to neoplastic progression. We investigate the expression patterns of extracellular matrix (ECM) molecules in Barrett's esophagus and Barrett's esophagus-related neoplasia, and assess their value as biomarkers for the diagnosis of Barrett's esophagus-related neoplasia and to predict neoplastic progression.
Experimental Design:
Gene-expression analyses of ECM matrisome gene sets were performed using publicly available data on human Barrett's esophagus, Barrett's esophagus-related dysplasia, esophageal adenocarcinoma (ADCA) and normal esophagus. Immunohistochemical expression of basement membrane (BM) marker agrin (AGRN) and p53 was analyzed in biopsies of Barrett's esophagus-related neoplasia from 321 patients in three independent cohorts.
Results:
Differential gene-expression analysis revealed significant enrichment of ECM matrisome gene sets in dysplastic Barrett's esophagus and ADCA compared with controls. Loss of BM AGRN expression was observed in both Barrett's esophagus-related dysplasia and ADCA. The mean AGRN loss in Barrett's esophagus glands was significantly higher in Barrett's esophagus-related dysplasia and ADCA compared with non-dysplastic Barrett's esophagus (NDBE; P < 0.001; specificity = 82.2% and sensitivity = 96.4%). Loss of AGRN was significantly higher in NDBE samples from progressors compared with non-progressors (P < 0.001) and identified patients who progressed to advanced neoplasia with a specificity of 80.2% and sensitivity of 54.8%. Moreover, the combination of AGRN loss and abnormal p53 staining identified progression to Barrett's esophagus-related advanced neoplasia with a specificity and sensitivity of 86.5% and 58.7%.
Conclusions:
We highlight ECM changes during Barrett's esophagus progression to neoplasia. BM AGRN loss is a novel diagnostic biomarker that can identify patients with NDBE at increased risk of developing advanced neoplasia.
Related Concept Videos
01:21Barrett Esophagus-I: Introduction
This constant acid exposure transforms the esophagus's pink mucosal lining (stratified squamous epithelium) into a type of lining more...
01:21Barrett Esophagus-II: Clinical Manifestations and Management
To diagnose Barrett's esophagus, healthcare providers often recommend an endoscopy for those showing symptoms of acid reflux. The procedure...
01:29Gastroesophageal Reflux Disease II: Clinical Features and Management
Clinical Manifestations
GERD presents itself in a multitude of ways, with symptoms varying from person to person. The hallmark symptoms are...
01:26Esophageal Strictures-II: Clinical Features and Management
Healthcare providers should gather a comprehensive medical history and conduct a physical examination for diagnosis. If esophageal stricture is...
01:30Esophageal Strictures-I: Introduction
Etiology
The primary cause of esophageal strictures is long-standing gastroesophageal reflux disease (GERD), accounting for about 70 to 80% of adult cases. Chronic acid reflux can lead to injury and scarring of the esophageal lining, culminating in...
01:28Peptic Ulcer Disease III: Clinical Manifestations and Diagnostic Studies
Few clinical manifestations differentiate gastric ulcers from duodenal ulcers. Distinctions in the location, timing, and pain relief are crucial for healthcare providers in differentiating between gastric and duodenal ulcers during clinical assessments.