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.

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