title: A study of indefinite for dysplasia in Barrett's oesophagus: reproducibility of diagnosis, clinical outcomes and predicting progression with AMACR (alpha-methylacyl-CoA-racemase).
abstract: OBJECTIVE
  To assess interobserver variation in the diagnosis of dysplasia in Barrett's oesophagus, especially indefinite dysplasia (IND) using the revised Vienna classification. A secondary aim was to study clinical outcome of IND cases and to evaluate expression of alpha-methyl-CoA racemase (AMACR) as a marker predictive of progression.
  
  
  RESULTS
  Cases of Barrett's oesophagus and dysplasia over a 20 year period were assessed. Three experienced histopathologists reviewed 101 cases on set criteria in a blinded fashion. Slides were immunostained for AMACR and evaluated for the presence, extent and location of AMACR expression. Clinical and progression data were collected. Overall agreement for the diagnosis of dysplasia was fair (k = 0.35) but that for IND was poor (k = 0.18). 6 IND cases progressed after a median follow-up of 31.4 months to a higher grade. The sensitivity of AMACR for the detection of abnormality was 22% for IND and specificity 100%. The positive predictive value of AMACR for progression was 0.44 and the negative predictive value was 0.92.
  
  
  CONCLUSIONS
  Fair agreement was achieved for the diagnosis of dysplasia but poor agreement for IND. A proportion of IND cases progress. Re-diagnosis or consensus diagnosis did not predict progression. AMACR shows promise as a marker to indicate IND patients in need of more intensive surveillance.
authors.affiliation: Calderdale and Huddersfield NHS Trust, Leeds, UK. sunil.sonwalkar@cht.nhs.uk
authors.forename: Sunil A
authors.initials: SA
authors.lastname: Sonwalkar
authors.forename: Olorunda
authors.initials: O
authors.lastname: Rotimi
authors.forename: Nigel
authors.initials: N
authors.lastname: Scott
authors.forename: Eldo
authors.initials: E
authors.lastname: Verghese
authors.forename: Mike
authors.initials: M
authors.lastname: Dixon
authors.forename: Anthony T R A
authors.initials: AT
authors.lastname: Axon
authors.forename: Simon M
authors.initials: SM
authors.lastname: Everett
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011230:Precancerous Conditions / Q000473:pathology*; D019998:Racemases and Epimerases / Q000378:metabolism*
chemical_list: D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase