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


METHODS
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.
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Massimiliano
M
di Pietro
Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands.
David F
DF
Boerwinkel
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Mohammed Kareem
MK
Shariff
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Xinxue
X
Liu
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands Digestive Disease Centre, NIHR Biomedical Research Unit, Nottingham University Hospitals NHS trust, Nottingham, UK Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands Department of Pathology, Nottingham University Hospitals NHS Trust, Nottingham, UK Biostatistics Unit, Medical Research Council, Cambridge, UK.
Emmanouil
E
Telakis
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Pierre
P
Lao-Sirieix
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Elaine
E
Walker
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
George
G
Couch
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Leanne
L
Mills
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Tara
T
Nuckcheddy-Grant
Digestive Disease Centre, NIHR Biomedical Research Unit, Nottingham University Hospitals NHS trust, Nottingham, UK.
Susan
S
Slininger
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Maria
M
O'Donovan
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Mike
M
Visser
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Sybren L
SL
Meijer
Department of Pathology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Philip V
PV
Kaye
Biostatistics Unit, Medical Research Council, Cambridge, UK.
Lorenz
L
Wernisch
Digestive Disease Centre, NIHR Biomedical Research Unit, Nottingham University Hospitals NHS trust, Nottingham, UK.
Krish
K
Ragunath
Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands.
Jacques J G H M
JJ
Bergman
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge, UK.
Rebecca C
RC
Fitzgerald
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis*; D003430:Cross-Sectional Studies; D004945:Esophagoscopy; D005260:Female; D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods; D008297:Male; D008875:Middle Aged; D061848:Optical Imaging; D011446:Prospective Studies
D015415:Biomarkers
Barrett's Oesophagus; Dysplasia; Endoscopy; Oesophageal Cancer; Surveillance