Detection of colorectal dysplasia using fluorescently labelled lectins

Abstract

Colorectal cancer screening using conventional colonoscopy lacks molecular information and can miss dysplastic lesions. We tested here the ability of fluorescently labelled lectins to distinguish dysplasia from normal tissue when sprayed on to the luminal surface epithelium of freshly resected colon tissue from the Apcmin mouse and when applied to fixed human colorectal tissue sections. Wheat germ agglutinin (WGA) showed significantly decreased binding to adenomas in the mouse tissue and in sections of human colon from 47 patients. Changes in WGA binding to the human surface epithelium allowed regions containing normal epithelium (NE) or hyperplastic polyps (HP) to be distinguished from regions containing low-grade dysplasia (LGD), high-grade dysplasia (HGD) or carcinoma (C), with 81% sensitivity, 87% specificity and 93% positive predictive value (PPV). Helix pomatia agglutinin (HGA) distinguished epithelial regions containing NE from regions containing HP, LGD, HGD or C, with 89% sensitivity, 87% specificity and 97% PPV. The decreased binding of WGA and HPA to the luminal surface epithelium in human dysplasia suggests that these lectins may enable more sensitive detection of disease in the clinic using fluorescence colonoscopy.

Fluorescence contrast-enhanced proliferative lesion imaging by enema administration of indocyanine green in a rat model of colon carcinogenesis

“…Vertical distribution of the ICG fluorescence, localized only at the colon tumor surface, was also observed (Figure 3B ). Fluorescence signal of wheat germ agglutinin (WGA), which binds to glycoproteins and is used for mucus imaging [ 35 ], was observed both in the tumor tissues and normal colonic mucosa (Figure 3C ).…”

Recapitulation of the accessible interface of biopsy-derived canine intestinal organoids to study epithelial-luminal interactions

“…To investigate the presence of physiological mucus production in the monolayer, live-cell staining with Wheat Germ Agglutinin (WGA) was performed [17,25,26]. We found that the WGA-positive signals were detected across the entire monolayer, suggesting that the epithelial apical surface was covered by mucus-like molecules such as N-acetyl-D-glucosamine ( Fig 4A).…”

Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications

“…Lectins are glycoproteins that bind to specific sugar residues (oligosaccharides) and have been developed to detect cell-surface glycans that are altered in cancer [ 90 , 109 ]. Unlike other posttranslational modifications, glycosylation is highly specific in cancer and provides a promising biomarker for early cancer detection [ 110 , 111 ].…”

“…WGA labeled with Alexa Fluor 647 (AF647, λ ex = 650 nm λ em = 668 nm) showed significantly decreased binding in sections of human colonic adenomas ex vivo ( Figure 8(a) ) [ 90 ]. This targeted contrast agent could distinguish among normal epithelium, hyperplastic polyps, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma with high sensitivity, specificity, and positive predictive value (Figures 8(b) and 8(c) ).…”

“…(b) Immunofluorescence of human colon, including (HP), low-grade dysplasia (LGD), high grade dysplasia (HGD), and adenocarcinoma (AC), is shown stained with lectin Helix pomatia agglutinin (HPA) labeled with AF647. (c) Corresponding histology (H&E) ((a) reprinted and modified with the permission from [ 111 ] and (b) reprinted with the permission from [ 90 ]).…”