Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study.

Autor:	Timmer MR; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Martinez P; Evolution and Cancer Laboratory, Centre for Tumour Biology, Barts Cancer Institute, London, UK., Lau CT; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Westra WM; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Calpe S; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Rygiel AM; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Rosmolen WD; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Meijer SL; Department of Pathology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Ten Kate FJ; Department of Pathology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Dijkgraaf MG; Clinical Research Unit, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Mallant-Hent RC; Department of Gastroenterology, Flevoziekenhuis, Almere, The Netherlands., Naber AH; Department of Gastroenterology, Tergooiziekenhuizen, Hilversum, The Netherlands., van Oijen AH; Department of Gastroenterology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands., Baak LC; Department of Gastroenterology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands., Scholten P; Department of Gastroenterology, Sint Lucas Andreas Ziekenhuis, Amsterdam, The Netherlands., Böhmer CJ; Department of Gastroenterology, Spaarne Ziekenhuis, Hoofddorp, The Netherlands., Fockens P; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Maley CC; Centre for Evolution and Cancer, University of California at San Francisco, San Francisco, California, USA., Graham TA; Evolution and Cancer Laboratory, Centre for Tumour Biology, Barts Cancer Institute, London, UK., Bergman JJ; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands., Krishnadath KK; Department of Gastroenterology and Hepatology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Gut [Gut] 2016 Oct; Vol. 65 (10), pp. 1602-10. Date of Electronic Publication: 2015 Jun 23.
DOI:	10.1136/gutjnl-2015-309642
Abstrakt:	Objective: The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. Methods: In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver operating characteristic curves and a leave-one-out analysis. Results: A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain and aneusomy, were significantly associated with progression on univariate analysis. We defined an 'Abnormal Marker Count' that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI 2.6 to 29.8) increased HR when compared with the low-risk group, with an area under the curve of 0.76 (95% CI 0.66 to 0.86). Conclusions: A prediction model based on age, Barrett's length and the markers p16, MYC and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
Databáze:	MEDLINE
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