title: Comparison of nuclear texture analysis and image cytometric DNA analysis for the assessment of dysplasia in Barrett's oesophagus.
abstract: BACKGROUND
  Dysplasia is a marker of cancer risk in Barrett's oesophagus (BO), but this risk is variable and diagnosis is subject to inter-observer variability. Cancer risk in BO is increased when chromosomal instability is present. Nucleotyping (NT) is a new method that uses high-resolution digital images of nuclei to assess chromatin organisation both quantitatively and qualitatively. We aimed to evaluate NT as a marker of dysplasia in BO and compare with image cytometric DNA analysis (ICM).
  
  
  METHODS
  In all, 120 patients with BO were studied. The non-dysplastic group (n=60) had specialised intestinal metaplasia only on two consecutive endoscopies after 51 months median follow-up (IQR=25-120 months). The dysplastic group (n=60) had high-grade dysplasia or carcinoma in situ. The two groups were then randomly assigned to a training set and a blinded test set in a 1:1 ratio. Image cytometric DNA analysis and NT was then carried out on Feulgen-stained nuclear monolayers.
  
  
  RESULTS
  The best-fit model for NT gave a correct classification rate (CCR) for the training set of 83%. The test set was then analysed using the same textural features and yielded a CCR of 78%. Image cytometric DNA analysis alone yielded a CCR of 73%. The combination of ICM and NT yielded a CCR of 84%.
  
  
  CONCLUSIONS
  Nucleotyping differentiates dysplastic and non-dysplastic BO, with a greater sensitivity than ICM. A combination score based on both techniques performed better than either test in isolation. These data demonstrate that NT/ICM on nuclear monolayers is a very promising single platform test of genomic instability, which may aid pathologists in the diagnosis of dysplasia and has potential as a biomarker in BO.
authors.affiliation: Department of Surgery, National Medical Laser Centre, University College London, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Dunn
authors.forename: T
authors.initials: T
authors.lastname: Hveem
authors.forename: M
authors.initials: M
authors.lastname: Pretorius
authors.forename: D
authors.initials: D
authors.lastname: Oukrif
authors.forename: B
authors.initials: B
authors.lastname: Nielsen
authors.forename: F
authors.initials: F
authors.lastname: Albregtsen
authors.forename: L B
authors.initials: LB
authors.lastname: Lovat
authors.forename: M R
authors.initials: MR
authors.lastname: Novelli
authors.forename: H E
authors.initials: HE
authors.lastname: Danielsen
mesh_terms: D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000235:genetics*; D006801:Humans; D011123:Polyploidy
chemical_list: D004247:DNA