Aneuploidy in targeted endoscopic biopsies outperforms other tissue biomarkers in the prediction of histologic progression of Barrett's oesophagus: A multi-centre prospective cohort study.
Adenocarcinoma
/ genetics
Aged
Aged, 80 and over
Aneuploidy
Barrett Esophagus
/ genetics
Core Binding Factor Alpha 3 Subunit
/ genetics
Cyclin A
/ genetics
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Disease Progression
Endoscopy
Esophageal Neoplasms
/ genetics
Female
Genetic Markers
Humans
Logistic Models
Male
Membrane Proteins
/ genetics
Middle Aged
Neoplasm Proteins
/ genetics
Prospective Studies
Tumor Suppressor Protein p53
/ genetics
Barrett's oesophagus
Biomarkers
Dysplasia
Histologic progression
Oesophageal adenocarcinoma
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
02
03
2020
revised:
02
04
2020
accepted:
08
04
2020
pubmed:
28
5
2020
medline:
13
4
2021
entrez:
28
5
2020
Statut:
ppublish
Résumé
The 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. 203 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. 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 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. Aneuploidy 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.
Sections du résumé
BACKGROUND
BACKGROUND
The 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.
METHODS
METHODS
203 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.
FINDINGS
RESULTS
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 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.
INTERPRETATION
CONCLUSIONS
Aneuploidy 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.
Identifiants
pubmed: 32460165
pii: S2352-3964(20)30140-7
doi: 10.1016/j.ebiom.2020.102765
pmc: PMC7251385
mid: EMS86189
pii:
doi:
Substances chimiques
CDKN2A protein, human
0
Core Binding Factor Alpha 3 Subunit
0
Cyclin A
0
Cyclin-Dependent Kinase Inhibitor p16
0
Genetic Markers
0
Membrane Proteins
0
Neoplasm Proteins
0
Runx3 protein, human
0
TMEFF2 protein, human
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
102765Subventions
Organisme : Medical Research Council
ID : MC_UU_12022/2
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest KR reports grants, personal fees and non-financial support from Olympus, outside the submitted work. JB reports grants from Olympus Endoscopy, outside the submitted work. Other authors have nothing to disclose.
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