Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus
- Florine Kastelein1,
- Katharina Biermann2,
- Ewout W Steyerberg3,
- Joanne Verheij4,
- Marit Kalisvaart1,
- Leendert H J Looijenga2,
- Hans A Stoop2,
- Laurens Walter2,
- Ernst J Kuipers1,5,
- Manon C W Spaander1,
- Marco J Bruno1,
- on behalf of the ProBar-study group
- 1Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
- 2Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands
- 3Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
- 4Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
- 5Department if Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
- Correspondence to Florine Kastelein, Department of Gastroenterology and Hepatology, Erasmus Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands;
- Received 22 August 2012
- Revised 29 November 2012
- Accepted 1 December 2012
- Published Online First 20 December 2012
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.
Design 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 (RRa) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RRa 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.