Barrett’s esophagus (BE) refers to the mucosal transition from normal squamous mucosa to a genetically unstable specialized columnar-type intestinal metaplasia in the esophagus. Recent sophisticated studies using orthogonal techniques of molecular and computational biology strongly support that BE is the predominant pathway to esophageal adenocarcinoma (EAC). In this treatise, we review the risk of BE transforming to EAC and the latest developments in risk assessment of BE progression to EAC. The progression rate of BE to EAC can vary from one study to another depending on the region of origin, definition of BE, and variations in data capture. Overall, the published studies suggest that the risk of BE transforming to EAC is less than 0.5% per year and that to high-grade dysplasia (HGD) or EAC is less than 1% per year. Clinical tools to predict risk such as the Progression in Barrett’s (PIB) have been developed but will need further validation. p53 is the biomarker for risk stratification and has stood the test of time but is still not being widely used due to incomplete correlation between the mutational status and protein expression. Molecular studies using genomics and proteomics approaches are being evaluated but need to demonstrate good clinical accuracy before being translated into practice.
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