title: Cyclin A immunocytology as a risk stratification tool for Barrett's esophagus surveillance.
abstract: OBJECTIVE
  Endoscopic surveillance of Barrett's esophagus (BE) by histopathologic biopsy assessment is suboptimal. A proliferation marker, minichromosome maintenance protein 2, has potential as a biomarker but lacks specificity. We hypothesized that cyclin A, which detects a proportion of proliferating cells, would be more specific. Because cytologic sampling has clinical advantages, we also evaluated the efficacy of cyclin A in endoscopic brushing samples.
  
  
  METHODS
  A cross-sectional cyclin A immunostaining study was done in 77 patients attending for BE surveillance and 17 patients undergoing evaluation of esophageal adenocarcinoma. The control tissues were as follows: 30 squamous esophagus, 20 gastric antrum, and 13 duodenum. A nested case-control study was done within the same surveillance cohort (16 progressors compared with 32 matched controls) to determine the relative risk for progression. Immunocytology was done for endoscopic brushings collected prospectively from 75 BE +/- dysplasia and 33 esophageal adenocarcinomas.
  
  
  RESULTS
  Surface expression of cyclin A in BE samples correlated with the degree of dysplasia (P = 0.016). In the case-control cohort, patients with biopsies expressing cyclin A at the surface were more likely to progress to adenocarcinoma than those who did not (odds ratio, 7.5; 95% confidence interval, 1.8-30.7). The sensitivity and specificity of cyclin A expression in brushings for the detection of high-grade dysplasia and cancer patients were 97.8% and 58.7%, respectively. The associated negative predictive value was 97.4%.
  
  
  CONCLUSIONS
  Cyclin A immunopositivity correlates with cancer risk. Application of this marker to endoscopic brushings could be used as a first step to identify BE patients with the highest risk of progression.
authors.affiliation: Medical Research Council-Cancer Cell Unit, Medical Research Council/Hutchison Research Centre, Hills Road, Cambridge, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lao-Sirieix
authors.forename: Laurence
authors.initials: L
authors.lastname: Lovat
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fitzgerald
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism*; D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000378:metabolism*; D014408:Biomarkers, Tumor; D001706:Biopsy; D016022:Case-Control Studies; D049109:Cell Proliferation; D015331:Cohort Studies; D019925:Cyclin A / Q000096:biosynthesis*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D012306:Risk; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D019925:Cyclin A