title: Population-based study reveals new risk-stratification biomarker panel for Barrett's esophagus.
abstract: OBJECTIVE
  The risk of progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is low and difficult to calculate. Accurate tools to determine risk are needed to optimize surveillance and intervention. We assessed the ability of candidate biomarkers to predict which cases of BE will progress to EAC or high-grade dysplasia and identified those that can be measured in formalin-fixed tissues.
  
  
  METHODS
  We analyzed data from a nested case-control study performed using the population-based Northern Ireland BE Register (1993-2005). Cases who progressed to EAC (n = 89) or high-grade dysplasia ≥ 6 months after diagnosis with BE were matched to controls (nonprogressors, n = 291), for age, sex, and year of BE diagnosis. Established biomarkers (abnormal DNA content, p53, and cyclin A expression) and new biomarkers (levels of sialyl Lewis(a), Lewis(x), and Aspergillus oryzae lectin [AOL] and binding of wheat germ agglutinin) were assessed in paraffin-embedded tissue samples from patients with a first diagnosis of BE. Conditional logistic regression analysis was applied to assess odds of progression for patients with dysplastic and nondysplastic BE, based on biomarker status.
  
  
  RESULTS
  Low-grade dysplasia and all biomarkers tested, other than Lewis(x), were associated with risk of EAC or high-grade dysplasia. In backward selection, a panel comprising low-grade dysplasia, abnormal DNA ploidy, and AOL most accurately identified progressors and nonprogressors. The adjusted odds ratio for progression of patients with BE with low-grade dysplasia was 3.74 (95% confidence interval, 2.43-5.79) for each additional biomarker and the risk increased by 2.99 for each additional factor (95% confidence interval, 1.72-5.20) in patients without dysplasia.
  
  
  CONCLUSIONS
  Low-grade dysplasia, abnormal DNA ploidy, and AOL can be used to identify patients with BE most likely to develop EAC or high-grade dysplasia.
authors: Medical Research Council Cancer Cell Unit, Hutchison-MRC Research Centre, Cambridge, United Kingdom.
authors: Elizabeth L
authors: EL
authors: Bird-Lieberman
authors: Jason M
authors: JM
authors: Dunn
authors: Helen G
authors: HG
authors: Coleman
authors: Pierre
authors: P
authors: Lao-Sirieix
authors: Dahmane
authors: D
authors: Oukrif
authors: Christina E
authors: CE
authors: Moore
authors: Sibu
authors: S
authors: Varghese
authors: Brian T
authors: BT
authors: Johnston
authors: Kenneth
authors: K
authors: Arthur
authors: Damian T
authors: DT
authors: McManus
authors: Marco R
authors: MR
authors: Novelli
authors: Maria
authors: M
authors: O'Donovan
authors: Christopher R
authors: CR
authors: Cardwell
authors: Laurence B
authors: LB
authors: Lovat
authors: Liam J
authors: LJ
authors: Murray
authors: Rebecca C
authors: RC
authors: Fitzgerald
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D000782:Aneuploidy; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D018395:CA-19-9 Antigen; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D019925:Cyclin A / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009660:Northern Ireland; D009844:Oligosaccharides / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D012372:ROC Curve; D012042:Registries; D018570:Risk Assessment; D000080506:Sialyl Lewis X Antigen; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014909:Wheat Germ Agglutinins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018395:CA-19-9 Antigen; D019925:Cyclin A; D037102:Lectins; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D016159:Tumor Suppressor Protein p53; D014909:Wheat Germ Agglutinins