title: Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus.
abstract: OBJECTIVE
  The value of surveillance for patients with Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of discriminative tests for risk stratification. Histological diagnosis of low-grade dysplasia (LGD) is the only accepted predictor for progression to date, but has a low predictive value. The aim of this study was therefore to evaluate the value of p53 immunohistochemistry for predicting neoplastic progression in patients with BO.
  
  
  METHODS
  We conducted a case-control study within a prospective cohort of 720 patients with BO. Patients who developed high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) were classified as cases and patients without neoplastic progression were classified as controls. P53 protein expression was determined by immunohistochemistry in more than 12 000 biopsies from 635 patients and was scored independently by two expert pathologists who were blinded to long-term outcome.
  
  
  RESULTS
  During follow-up, 49 (8%) patients developed HGD or OAC. P53 overexpression was associated with an increased risk of neoplastic progression in patients with BO after adjusting for age, gender, Barrett length and oesophagitis (adjusted relative risks (RR(a)) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RR(a) 14.0; 95% CI 5.3 to 37.2). The positive predictive value for neoplastic progression increased from 15% with histological diagnosis of LGD to 33% with LGD and concurrent aberrant p53 expression.
  
  
  CONCLUSIONS
  Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, , Rotterdam, The Netherlands.
authors.forename: Florine
authors.initials: F
authors.lastname: Kastelein
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.forename: Marit
authors.initials: M
authors.lastname: Kalisvaart
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
authors.forename: Hans A
authors.initials: HA
authors.lastname: Stoop
authors.forename: Laurens
authors.initials: L
authors.lastname: Walter
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Manon C W
authors.initials: MC
authors.lastname: Spaander
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Bruno
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000368:Aged; D001471:Barrett Esophagus / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53