Abstract LB-122: molecular imaging of early colorectal dysplasia using fluorescently-labeled lectins

Abstract

Abstract Objective Screening for colorectal cancer (CRC) is currently performed using bright-field colonoscopy, which has low specificity and sensitivity for the detection of early dysplasia in the colon. Fluorescently labeled lectins have been applied topically for detecting glycosylation changes in early dysplastic lesions in the esophagus, providing a route for improved endoscopic detection using fluorescence endoscopy [1]. We have identified here fluorescently labeled lectins that can detect changes in glycosylated biomarkers on the surface epithelium of early dysplasia in CRC. These probes may enable fluorescence-guided resection of dysplastic lesions at colonoscopy and subsequent automated assessment of colon histopathology. Study Design Ninety-nine colon lesions in 48 patients (34 males, 14 females; mean patient age 68.8 ± 8.3 yr, range 53-95 yr) were identified during routine colonoscopy at Addenbrooke's Hospital, Cambridge, UK. Lesions suspected of being dysplastic or neoplastic, were detected using magnification colonoscopy or surgery, and removal performed at biopsy (11.7%) and/or polypectomy (62.1%), or partial colon resection (11.7%). Colon histological sections were stained with fluorescently labeled lectins, and the lectin binding to surface epithelium, which would be observable in colonoscopy, was compared with conventional histopathology for the presence of disease and disease stage. Results Normal colonic epithelium (NE) occupied 40.1% of the area of all sections, hyperplastic polyps (HP) occupied 10.2%, low- (LGD) dysplasia 25.6%, high-grade (HGD) dysplasia 13.9%, and adenocarcinoma (C) 10.2%, as assessed by conventional histopathology based on H&E staining. Lesions were located in the ascending (10.4%), transverse (15.6%), descending (14.3%), sigmoid (42.9%) colon and rectum (7.8%), with the mean lesion size being 16.0 ± 14.2 mm (range 2-60 mm). The lectin wheat germ agglutinin (WGA), when fluorescently-labeled, was capable of distinguishing epithelial regions containing NE from regions containing LGD, HGD and cancer, with >81% sensitivity, >79% specificity and >93% positive predictive value. Conclusions Automated analysis of fluorescently-labeled WGA binding to the surface epithelium of excised colon sections may be used for improving the assessment of early dysplasia in CRC. The same fluorescent lectin may also be useful as a topical imaging agent for improving detection of early dysplasia using fluorescence colonoscopy, increasing the early diagnosis of CRC and improving patient survival.