Abstract
Barrett's esophagus is an example of a pre-invasive state, for which current endoscopic surveillance methods to detect dysplasia are time consuming and inadequate. The prognosis of cancer arising in Barrett's esophagus is improved by early detection at the stage of mucosal carcinoma or high-grade dysplasia. Molecular imaging methods could revolutionize the detection of dysplasia, provided they permit a wide field of view and highlight abnormalities in real time. We show here that cell-surface glycans are altered in the progression from Barrett's esophagus to adenocarcinoma and lead to specific changes in lectin binding patterns. We chose wheat germ agglutinin as a candidate lectin with clinical potential. The binding of wheat germ agglutinin to human tissue was determined to be specific, and we validated this specific binding by successful endoscopic visualization of high-grade dysplastic lesions, which were not detectable by conventional endoscopy, with a high signal-to-background ratio of over 5.
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References
Cook, M.B., Chow, W.H. & Devesa, S.S. Oesophageal cancer incidence in the United States by race, sex, and histologic type, 1977–2005. Br. J. Cancer 101, 855–859 (2009).
Enzinger, P.C. & Mayer, R.J. Esophageal cancer. N. Engl. J. Med. 349, 2241–2252 (2003).
Reid, B.J. et al. Predictors of progression to cancer in Barrett's esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets. Am. J. Gastroenterol. 95, 1669–1676 (2000).
Shaheen, N.J. et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N. Engl. J. Med. 360, 2277–2288 (2009).
Spechler, S.J., Fitzgerald, R.C., Prasad, G.A. & Wang, K.K. History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus. Gastroenterology 138, 854–869 (2010).
Reid, B.J. et al. Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions. Gastroenterology 94, 81–90 (1988).
Reid, B.J., Blount, P.L., Feng, Z. & Levine, D.S. Optimizing endoscopic biopsy detection of early cancers in Barrett's high-grade dysplasia. Am. J. Gastroenterol. 95, 3089–3096 (2000).
Curvers, W.L. et al. Endoscopic trimodal imaging versus standard video endoscopy for detection of early Barrett's neoplasia: a multicenter, randomized, crossover study in general practice. Gastrointest. Endosc. 73, 195–203 (2010).
Pohl, H. et al. Miniprobe confocal laser microscopy for the detection of invisible neoplasia in patients with Barrett's oesophagus. Gut 57, 1648–1653 (2008).
Pyhtila, J.W. et al. In situ detection of nuclear atypia in Barrett's esophagus by using angle-resolved low-coherence interferometry. Gastrointest. Endosc. 65, 487–491 (2007).
Kendall, C. et al. Raman spectroscopy, a potential tool for the objective identification and classification of neoplasia in Barrett's oesophagus. J. Pathol. 200, 602–609 (2003).
Evans, J.A. et al. Identifying intestinal metaplasia at the squamocolumnar junction by using optical coherence tomography. Gastrointest. Endosc. 65, 50–56 (2007).
Lovat, L.B. et al. Elastic scattering spectroscopy accurately detects high grade dysplasia and cancer in Barrett's oesophagus. Gut 55, 1078–1083 (2006).
Reid, B.J., Li, X., Galipeau, P.C. & Vaughan, T.L. Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat. Rev. Cancer 10, 87–101 (2010).
Hsiung, P.L. et al. Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy. Nat. Med. 14, 454–458 (2008).
Li, M. et al. Affinity peptide for targeted detection of dysplasia in Barrett's esophagus. Gastroenterology 139, 1472–1480 (2010).
Fuster, M.M. & Esko, J.D. The sweet and sour of cancer: glycans as novel therapeutic targets. Nat. Rev. Cancer 5, 526–542 (2005).
Laughlin, S.T. & Bertozzi, C.R. Imaging the glycome. Proc. Natl. Acad. Sci. USA 106, 12–17 (2009).
Miyake, M., Taki, T., Hitomi, S. & Hakomori, S. Correlation of expression of H/Le(y)/Le(b) antigens with survival in patients with carcinoma of the lung. N. Engl. J. Med. 327, 14–18 (1992).
Peters, C.J. et al. A 4-gene signature predicts survival of patients with resected adenocarcinoma of the esophagus, junction, and gastric cardia. Gastroenterology 139, 1995–2004.e15 (2010).
Dennis, J., Waller, C., Timpl, R. & Schirrmacher, V. Surface sialic acid reduces attachment of metastatic tumour cells to collagen type IV and fibronectin. Nature 300, 274–276 (1982).
Nagata, Y. & Burger, M.M. Wheat germ agglutinin. Isolation and crystallization. J. Biol. Chem. 247, 2248–2250 (1972).
Pilobello, K.T., Slawek, D.E. & Mahal, L.K. A ratiometric lectin microarray approach to analysis of the dynamic mammalian glycome. Proc. Natl. Acad. Sci. USA 104, 11534–11539 (2007).
Kuno, A. et al. Evanescent-field fluorescence-assisted lectin microarray: a new strategy for glycan profiling. Nat. Methods 2, 851–856 (2005).
Kronis, K.A. & Carver, J.P. Specificity of isolectins of wheat germ agglutinin for sialyloligosaccharides: a 360-MHz proton nuclear magnetic resonance binding study. Biochemistry 21, 3050–3057 (1982).
Medarova, Z., Rashkovetsky, L., Pantazopoulos, P. & Moore, A. Multiparametric monitoring of tumor response to chemotherapy by noninvasive imaging. Cancer Res. 69, 1182–1189 (2009).
Kobayashi, H. et al. Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation. Clin. Cancer Res. 10, 7712–7720 (2004).
Soukos, N.S. et al. Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo. Cancer Res. 61, 4490–4496 (2001).
Yogeeswaran, G. & Salk, P.L. Metastatic potential is positively correlated with cell surface sialylation of cultured murine tumor cell lines. Science 212, 1514–1516 (1981).
Shen, Y., Tiralongo, J., Kohla, G. & Schauer, R. Regulation of sialic acid O-acetylation in human colon mucosa. Biol. Chem. 385, 145–152 (2004).
Gabor, F., Bogner, E., Weissenboeck, A. & Wirth, M. The lectin-cell interaction and its implications to intestinal lectin-mediated drug delivery. Adv. Drug Deliv. Rev. 56, 459–480 (2004).
Themelis, G. et al. Novel multispectral method for simultaneous color and fluorescence endoscopy. in Biomedical Optics, OSA Technical Digest (CD) (Optical Society of America, 2010), BTuD2064 (2010).
Qiu, L. et al. Multispectral scanning during endoscopy guides biopsy of dysplasia in Barrett's esophagus. Nat. Med. 16, 603–606 (2010).
Acknowledgements
This work was supported by a research fellowship from GlaxoSmithKline awarded to E.L.B.-L. The authors thank J. Ong, C. Peters, S. Hilborne, E. Moore, N. Shannon, B. Spencer, R. Cayado-Lopez, B. Haynes, J. Gray, W. Howat, J. Harris and S. Reichelt for their advice and support and the Moritex Corporation for lending the evanescent lectin array equipment (Glycostation). This work was supported by a Medical Research Centre core grant (R.C.F.), the Cambridge Experimental Medicine Centre (R.C.F.), the National Institute for Health Research Cambridge Biomedical Research Centre (R.C.F.), a Cancer Research UK core grant (K.M.B.) and a Clinical Research Fellowship from GlaxoSmithKline (E.L.B.-L.). The work undertaken in the Department of Chemistry, University of New York was supported by a New York University startup fund and by the US National Institutes of Health (W.S.E. and L.K.M.). The work undertaken at UCLH/UCL was supported in part by funding from the Department of Health's NIHR Biomedical Research Centre's funding scheme and also by a grant from Cancer Research UK to the Experimental Cancer Research Centre, UCL. The views expressed in this publication are those of the authors and not necessarily those of the UK Department of Health.
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E.L.B.-L. performed the experimental work and data analysis with help from A.A.N., P.L.-S. and L.K.M. M.O. and M.N. performed histopathological analyses. L.K.M. and W.S.E. applied prepared samples for the ratiometric array, and L.B.L. provided samples. R.C.F. and K.M.B. conceived of and supervised this work. The manuscript was written by E.L.B.-L. and R.C.F.
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Bird-Lieberman, E., Neves, A., Lao-Sirieix, P. et al. Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett's esophagus. Nat Med 18, 315–321 (2012). https://doi.org/10.1038/nm.2616
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DOI: https://doi.org/10.1038/nm.2616