Diagnosis and risk stratification of Barrett's dysplasia by flow cytometric DNA analysis of paraffin-embedded tissue
Journal
Gut
Journal Volume
67
Journal Issue
7
Pages
1229-1238
Date Issued
2018
Author(s)
Abstract
Objective The diagnosis of dysplasia in Barrett's oesophagus (BO) can be challenging, and reliable ancillary techniques are not available. This study examines if DNA content abnormality detected by flow cytometry can serve as a diagnostic marker of dysplasia and facilitate risk stratification of low-grade dysplasia (LGD) and indefinite for dysplasia (IND) patients using formalin-fixed paraffin-embedded (FFPE) BO samples with varying degrees of dysplasia. Design D N A flow cytometry was performed on 80 FFPE BO samples with high-grade dysplasia (HGD), 38 LGD, 21 IND and 14 negative for dysplasia (ND). Three to four 60-micron thick sections were cut from each tissue block, and the area of interest was manually dissected. results DNA content abnormality was identified in 76 HGD (95%), 8 LGD (21.1%), 2 IND (9.5%) and 0 ND samples. As a diagnostic marker of HGD, the estimated sensitivity and specificity of DNA content abnormality were 9 5 % and 8 5 %, respectively. For patients with DNA content abnormality detected at baseline LGD or IND, the univariate HRs for subsequent detection of HGD or oesophageal adenocarcinoma (OAc) were 7.0 and 20.0, respectively (p =<0.001). Conclusions This study demonstrates the promise of DNA flow cytometry using FFPE tissue in the diagnosis and risk stratification of dysplasia in BO. The presence of DNA content abnormality correlates with increasing levels of dysplasia, as 9 5 % of HGD samples showed DNA content abnormality. DNA flow cytometry also identifies a subset of patients with LGD and IN D who are at higher risk for subsequent detection of HGD or OAC. ? Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved.
SDGs
Other Subjects
DNA; paraffin; adult; aged; Article; Barrett dysplasia; Barrett esophagus; controlled study; disease marker; disease severity; DNA determination; esophageal adenocarcinoma; esophagus disease; female; flow cytometry; human; human tissue; major clinical study; male; paraffin embedding; priority journal; risk assessment; sensitivity and specificity; adenocarcinoma; case control study; esophagus tumor; middle aged; pathology; risk assessment; very elderly; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Case-Control Studies; Esophageal Neoplasms; Female; Flow Cytometry; Humans; Male; Middle Aged; Paraffin Embedding; Risk Assessment; Sensitivity and Specificity
Publisher
BMJ Publishing Group
Type
journal article