Early Detection Research Network


Esophageal adenocarcinoma risk in Barrett's esophagus is increased 30- to 125- fold versus the general population. Among all Barrett's esophagus patients neoplastic progression occurs only once per 200 patient-years. Molecular markers (individual or in panel) would be useful to risk-stratify patients for more efficient surveillance endoscopy and to improve the early detection of progression. In 2005, Meltzer et al reported that hypermethylation of p16, RUNX3, and HPP1 occurs early in Barrett's esophagus-associated neoplastic progression and predicts risk. Later, the group developed a tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features, and also studied methylation levels and frequencies of individual genes using real-time quantitative methylation-specific PCR in 259 endoscopic esophageal biopsy specimens of different histologies. Among ten genes evaluated, five (NELL1, TAC1, SST, AKAP12, and CDH13) were methylated early and often in Barrett's esophagus-associated progression. In these studies, methylation status and levels correlated inversely with mRNA expression levels.
Under Review
The findings of this study suggest that this eight-marker panel is more objective and quantifiable and possesses higher predictive sensitivity and specificity than do clinical features, including age.
Barrett's Esophagus Methylation Profiles

We propose a nested case-control study of biomarkers in the setting of BE. By bringing together research institutions with large populations of patients with BE, we will perform a multi-center study of FISH and hypermethylation markers as possible prognostic factors in BE. The centers will select from their cohorts who have progressed to HGD or to adenocarcinoma of the esophagus ("progressors"), and who also donated samples prior to the development of cancer, when their histology was felt to be benign. These subjects will be compared to individuals who have been under endoscopic surveillance, but who have not progressed to HGD or EAC ("non-progressors"). Using this approach, we hope to identify promising markers for risk stratification in BE. We expect to be able to make successful application for a prospective study of markers identified in this case-control study.