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Original Article
Diagnosis and risk stratification of Barrett’s dysplasia by flow cytometric DNA analysis of paraffin-embedded tissue
  1. Won-Tak Choi1,
  2. Jia-Huei Tsai2,
  3. Peter S Rabinovitch3,
  4. Thomas Small3,
  5. Danning Huang4,
  6. Aras N Mattis1,
  7. Sanjay Kakar1
  1. 1Department of Pathology, University of California at San Francisco, San Francisco, California, USA
  2. 2Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
  3. 3Department of Pathology, University of Washington, Seattle, Washington, USA
  4. 4Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
  1. Correspondence to Dr Won-Tak Choi, Department of Pathology, University of California at San Francisco, 505 Parnassus Avenue, M552, Box 0102, San Francisco, CA 94143, USA; Won-Tak.Choi{at}ucsf.edu

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 DNA 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 95% and 85%, 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 95% of HGD samples showed DNA content abnormality. DNA flow cytometry also identifies a subset of patients with LGD and IND who are at higher risk for subsequent detection of HGD or OAC.

  • Aneuploidy
  • Barrett’s esophagus
  • DNA flow cytometry
  • dysplasia
  • esophageal adenocarcinoma

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Footnotes

  • Contributors W-TC, J-HT, PSR, ANM and SK contributed to the study concept and design, analysis and interpretation of data, and drafting of the manuscript. W-TC, J-HT and TS performed the experiments. DH contributed to analysis and interpretation of data as well as statistical analysis. All authors have read and approved the manuscript for publication.

  • Funding UCSF Department of Pathology.

  • Competing interests None declared.

  • Ethics approval University of California at San Francisco (UCSF).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with 'BMJ Publishing Group'. This only affected the full text version, not the PDF. We have since corrected these errors and the correct publishers have been inserted into the references.

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