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Sugar molecules enabled efficient detection of precancerous cells in esophagus
Bird-Lieberman EL. Nat Med. 2012;doi:10.1038/nm.2616.
Researchers have identified changes in the patterns of glycans, or sugar molecules, that line precancerous cells in the esophagus, allowing easier detection and removal of the cells before cancer progression, according to study results published in the journal Nature Medicine.
Patients with Barrett’s esophagus are currently screened for the presence of dysplasia or early-stage cancers through endoscopy and biopsies every 3 years — a prognosis that could be improved by early detection of mucosal carcinoma or high-grade dysplasia.
In this study, researchers examined the use of protein-specific molecular imaging methods that would permit early detection of precancerous markers in patients with Barrett’s esophagus.
“The rise in cases of esophageal cancer both in the U.K. and throughout the Western world means that it is increasingly important to find ways of detecting it as early as possible,” researcher Rebecca Fitzgerald, PhD, of the MRC Cancer Cell Unit in Cambridge, said in a press release. “Our work has many potential benefits for those with Barrett’s esophagus who have an increased risk of developing esophageal cancer.”
After analyzing the sugars present in human tissue samples obtained from various stages of cancer progression, researchers found that there were different glycans present on the surface of precancerous cells. Because glycans have large structures and have been revealed to be altered in cancers — including pancreatic, colon and stomach cancers — researchers theorized that these structures could be used as molecular targets for the endoscopic imaging of mucosal surfaces.
On this basis, researchers employed a molecular imaging approach in which fluorescence endoscopy and fluorescently labeled wheat germ proteins were used to detect changes in glycan expression on the cell surface that accompany the transition from Barrett’s esophagus through dysplasia to esophageal adenocarcinoma in situ.
After the study analysis, four glycan pathways were revealed to exhibit coordinated increases in the expression of genes encoding proteins involved in the biosynthesis and degradation of glycan structures in the progression to esophageal adenocarcinoma. The pathway for glycan degradation was supplemented during the metaplastic transition to Barrett’s esophagus, but the majority of augmentation in the glycosphingolipid pathway lactoseries took place as Barrett’s esophagus progressed to low-grade dysplasia and neo-lactoseries increased between low-grade dysplasia and high-grade dysplasia.
This study demonstrates that coordinated changes in glycan expression begin before the development of esophageal adenocarcinoma and provides a potential biomarker for the detection of dysplasia and the identification of those at risk of progression from Barrett’s esophagus to esophageal adenocarcinoma, according to researchers.
“We have demonstrated that binding of a wheat germ protein, which is cheap and nontoxic, can identify differences in surface sugars on precancerous cells,” Fitzgerald said. “When coupled with fluorescence imaging using an endoscopic camera, this technique offers a promising new way of finding and then treating patients with the highest risk of developing esophageal cancer, at the earliest stage.”
Disclosure: The researchers report no relevant financial disclosures.
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Barrett's esophagus is a precursor lesion in most cases of esophageal adenocarcinoma, with intermediate stages of low- and high-grade dysplasia occurring prior to the development of fully invasive cancer. For patients with known Barrett's esophagus, endoscopic surveillance at periodic intervals is recommended; however, the cost-effectiveness of this strategy remains controversial, particularly since individuals without dysplasia may in fact have a smaller risk of developing adenocarcinoma than previously estimated. Moreover, endoscopic surveillance with biopsies is prone to sampling error, thus increasing the risk of false-negative results. The current study demonstrates the promise of a fascinating new endoscopic technology, exploiting the fact that alterations in glycans — polysaccharides — take place on the surface of epithelial cells during the progression from Barrett's esophagus to invasive adenocarcinoma. The investigators show that fluorescein-labeled wheat germ agglutinin can be sprayed topically over the area of concern, allowing one to use a fluorescence endoscope to distinguish between areas of high-grade dysplasia/invasive carcinoma vs. nondysplastic or normal tissue. The potential implications of this technology in terms of guiding areas to biopsy and ablate in patients with Barrett's can be readily envisioned.
Obviously, though, much more work needs to be done before this approach can reach routine application. In this study, numbers were small, and the analyses were performed on esophageal specimens that were already resected. Hence, the next step will be a pilot study to test this technique in vivo in subjects with Barrett's esophagus at various stages. Nevertheless, given that proof of principle has been established with this innovative strategy, this and other molecular imaging tools mean that the future in Barrett's esophagus screening looks brighter — both literally and figuratively.
Andrew H. Ko, MD
HemOnc Today Editorial Board member
Disclosure: Dr. Ko reports no relevant financial disclosures.
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