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The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett's oesophagus.

Published version
Peer-reviewed

Type

Article

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Authors

di Pietro, Massimiliano 
Boerwinkel, David F 
Shariff, Mohammed Kareem 
Liu, Xinxue 
Telakis, Emmanouil 

Abstract

OBJECTIVE: Endoscopic surveillance for Barrett's oesophagus (BO) is limited by sampling error and the subjectivity of diagnosing dysplasia. We aimed to compare a biomarker panel on minimal biopsies directed by autofluorescence imaging (AFI) with the standard surveillance protocol to derive an objective tool for dysplasia assessment. DESIGN: We performed a cross-sectional prospective study in three tertiary referral centres. Patients with BO underwent high-resolution endoscopy followed by AFI-targeted biopsies. 157 patients completed the biopsy protocol. Aneuploidy/tetraploidy; 9p and 17p loss of heterozygosity; RUNX3, HPP1 and p16 methylation; p53 and cyclin A immunohistochemistry were assessed. Bootstrap resampling was used to select the best diagnostic biomarker panel for high-grade dysplasia (HGD) and early cancer (EC). This panel was validated in an independent cohort of 46 patients. RESULTS: Aneuploidy, p53 immunohistochemistry and cyclin A had the strongest association with dysplasia in the per-biopsy analysis and, as a panel, had an area under the receiver operating characteristic curve of 0.97 (95% CI 0.95 to 0.99) for diagnosing HGD/EC. The diagnostic accuracy for HGD/EC of the three-biomarker panel from AFI+ areas was superior to AFI- areas (p<0.001). Compared with the standard protocol, this panel had equal sensitivity for HGD/EC, with a 4.5-fold reduction in the number of biopsies. In an independent cohort of patients, the panel had a sensitivity and specificity for HGD/EC of 100% and 85%, respectively. CONCLUSIONS: A three-biomarker panel on a small number of AFI-targeted biopsies provides an accurate and objective diagnosis of dysplasia in BO. The clinical implications have to be studied further.

Description

Keywords

Barrett's Oesophagus, Dysplasia, Endoscopy, Oesophageal Cancer, Surveillance, Adult, Aged, Aged, 80 and over, Barrett Esophagus, Biomarkers, Cross-Sectional Studies, Esophagoscopy, Female, Humans, Image-Guided Biopsy, Male, Middle Aged, Optical Imaging, Prospective Studies

Journal Title

Gut

Conference Name

Journal ISSN

0017-5749
1468-3288

Volume Title

64

Publisher

BMJ
Sponsorship
TCC (None)
Medical Research Council (MC_UU_12022/2)