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

• Published in: Gut Vol. 64; no. 1; pp. 49 - 56
• Main Authors: di Pietro, Massimiliano, Boerwinkel, David F, Shariff, Mohammed Kareem, Liu, Xinxue, Telakis, Emmanouil, Lao-Sirieix, Pierre, Walker, Elaine, Couch, George, Mills, Leanne, Nuckcheddy-Grant, Tara, Slininger, Susan, O'Donovan, Maria, Visser, Mike, Meijer, Sybren L, Kaye, Philip V, Wernisch, Lorenz, Ragunath, Krish, Bergman, Jacques J G H M, Fitzgerald, Rebecca C
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.01.2015; BMJ Publishing Group
• Series: Original article
• Subjects: Accuracy; Adult; Aged; Aged, 80 and over; Barrett Esophagus - pathology; Biomarkers; Biomarkers - analysis; Biomedical research; Biopsy; Cancer; Clinical medicine; Cross-Sectional Studies; Endoscopy; Esophagoscopy; Female; Humans; Image-Guided Biopsy - methods; Laboratories; Male; Middle Aged; Optical Imaging; Patients; Prospective Studies; Studies; Surveillance; Dysplasia; Endoscopy; Surveillance; Barrett's Oesophagus; Oesophageal Cancer
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2013-305975

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.