Still waiting for predictive biomarkers in Barrett's oesophagus

Abstract

Barrett's oesophagus is important as a precursor of oesophageal adenocarcinoma via a metaplasia-dysplasia-carcinoma sequence. It is often detected on upper gastrointestinal endoscopy. In the absence of glandular dysplasia the risk of progression to cancer is low but ascertainment of dysplasia is not always straightforward. Sparse mucosal sampling may miss dysplasia, or reactive changes may be overinterpreted due to inter and intraobserver variation. Low-grade and even high-grade dysplasia do not necessarily progress, provided prevalent cancer has been rigorously excluded. This indeterminacy motivates an ongoing search for clinically useful predictive biomarkers. Although many genetic and epigenetic abnormalities have been associated with neoplastic progression in Barrett's mucosa no molecular tests have as yet been accepted into routine pathology practice. Challenges of assay definition remain and many marker studies lack statistical power or have other methodological flaws. Even where strong evidence of clinically relevant predictive value does exist (in the case of ploidy analysis by flow or image cytometry) adoption has been minimal, likely reflecting technological and possible reimbursement obstacles. Well designed multicentre studies are likely to be required to translate improved knowledge of Barrett's carcinogenesis into clinically significant progress on predictive testing, and will require a degree of cooperation not so far widely seen in the field.