Abstract

BackgroundThe cancer risk in Barrett's oesophagus (BO) is difficult to estimate. Histologic dysplasia has strong predictive power, but can be missed by random biopsies. Other clinical parameters have limited utility for risk stratification. We aimed to assess whether a molecular biomarker panel on targeted biopsies can predict neoplastic progression of BO.Methods203 patients with BO were tested at index endoscopy for 9 biomarkers (p53 and cyclin A expression; aneuploidy and tetraploidy; CDKN2A (p16), RUNX3 and HPP1 hypermethylation; 9p and 17p loss of heterozygosity) on autofluorescence-targeted biopsies and followed-up prospectively. Data comparing progressors to non-progressors were evaluated by univariate and multivariate analyses using survival curves, Cox-proportional hazards and logistic regression models.Findings127 patients without high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) at index endoscopy were included, of which 42 had evidence of any histologic progression over time. Aneuploidy was the only predictor of progression from non-dysplastic BO (NDBO) to any grade of neoplasia (p = 0.013) and HGD/OAC (p = 0.002). Aberrant p53 expression correlated with risk of short-term progression within 12 months, with an odds ratio of 6.0 (95% CI: 3.1–11.2). A panel comprising aneuploidy and p53 had an area under the receiving operator characteristics curve of 0.68 (95% CI: 0.59–0.77) for prediction of any progression.InterpretationAneuploidy is the only biomarker that predicts neoplastic progression of NDBO. Aberrant p53 expression suggests prevalent dysplasia, which might have been missed by random biopsies, and warrants early follow up.

Highlights

  • Barrett’s oesophagus (BO) is a precancerous lesion to oesophageal adenocarcinoma (OAC) that affects approximately 1.5À2.0% of the Western population [1À3]

  • We show that aberrant p53 correlates with short-term neoplastic progression, suggesting a high risk of histologically missed dysplasia at the time of a negative endoscopy

  • 76 (37.4%) patients were excluded from the final analysis due to either the presence of high-grade dysplasia (HGD) or OAC at baseline (n = 46), or treatment received for prevalent low-grade dysplasia (LGD) in the form of RFA or EMR (n = 11) or to lack of follow-up endoscopy due to old age, comorbidities, relocation to a different city or death (n = 19) (Fig. 1), leaving 127 (62.6%) patients for inclusion in the final analysis

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Summary

Introduction

Barrett’s oesophagus (BO) is a precancerous lesion to oesophageal adenocarcinoma (OAC) that affects approximately 1.5À2.0% of the Western population [1À3]. The annual cancer progression rate of non-dysplastic BO (NDBO) is estimated to be around 0.3%/year [9,10], it increases dramatically in the presence of dysplasia [10À14]. We aimed to assess whether a molecular biomarker panel on targeted biopsies can predict neoplastic progression of BO. Findings: 127 patients without high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) at index endoscopy were included, of which 42 had evidence of any histologic progression over time. Aneuploidy was the only predictor of progression from non-dysplastic BO (NDBO) to any grade of neoplasia (p = 0.013) and HGD/OAC (p = 0.002). Aberrant p53 expression suggests prevalent dysplasia, which might have been missed by random biopsies, and warrants early follow up

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