Detection of early oesophageal dysplasic change by molecular biomarker expression

▶ Bird-Lieberman EL, Neves AA, Lao-Sirieix P, et al. Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett's esophagus. Nat Med 2012;18:315–22.

The incidence of oesophageal adenocarcinoma is increasing and traditionally carries a poor prognosis. Barrett's oesophagus is a pre-malignant phenotype, and currently, the surveillance strategy for detecting disease progression involves repeat standard endoscopy with biopsies. This approach is the focus of continued controversy and debate. The problem is that small dysplastic foci are difficult to detect macroscopically and are often missed by quadrantic biopsies. This paper reports on a novel, fluorescently labelled, specific molecular detection strategy to identify dysplastic oesophageal epithelium associated with Barrett's oesophagus. Glycans are expressed on the epithelial cell surface, and initial genetic analysis in human samples revealed an aberrant expression pattern in dysplastic oesophageal cells. The pattern of glycan expression was then detected by specific binding of lectin probes to this molecular target. Validation data generated by gene array and immunohistochemistry revealed that the lectin-binding pattern is associated with degree of cell dysplasia. Binding of a specific lectin, WGA, was negatively correlated to progression from Barrett's epithelia to low-grade dysplasia to high-grade dysplasia, and was not influenced by degree of inflammation associated with reflux. This was then tested in vivo on four fresh human oesophagectomy specimens, each containing differing levels of histological dysplastic change. A fluorescein-labelled lectin was sprayed topically onto the mucosal surface and then imaged using a fluorescent endoscope. There was a highly significant correlation between histology and fluorescent lectin staining to detect dysplasia, including areas not macroscopically visible with standard white light endoscopy. This strategy may allow specific areas to be targeted for biopsy and subsequent endoscopic treatment. The authors discuss that some additional exploration of this is required, such as toxicity, and determination …