Expression of p53 predicts risk of prevalent and incident advanced neoplasia in patients with Barrett's esophagus and epithelial changes indefinite for dysplasia

Background and aims: Patients with Barrett's esophagus (BE) are at an increased risk for developing esophageal adenocarcinoma (EAC); thus they may undergo regular endoscopic surveillance. If epithelial changes cannot be unequivocally classified as negative or positive for dysplasia, a diagnosis of indefinite for dysplasia (IND) is recommended. Several biomarkers have been proposed as markers or predictors of neoplasia in the general BE population; however, their significance is not clear in patients with BE-IND. We therefore performed a retrospective study to determine whether expression of these biomarkers was associated with the development of neoplasia in BE-IND patients. Methods: We searched our archives to identify all cases of BE-IND diagnosed between January 1992 and December 2007. Immunohistochemical analyses were used to semi-quantify the expression of p53, alpha-methylacyl-CoA racemase (AMACR), and cyclin D1. A univariate analysis was used to identify predictors for prevalent and incident neoplasia and advanced neoplasia. Results: Among the 103 patients with an index diagnosis of BE-IND who were included in this study, 81 (78.6%) underwent a follow-up biopsy within 12 months of diagnosis; 10 (12.3%) had neoplasia, including four (4.9%) with advanced neoplasia. Among 79 patients without prevalent neoplasia who underwent more than 1 year of follow-up, 18 (22.8%) had developed neoplasia, including four (5.1%) with advanced neoplasia. AMACR and cyclin D1 expression levels were not correlated with prevalent or incident neoplasia; however, high p53 expression (>5%) was associated with prevalent advanced neoplasia on surveillance biopsy (P = 0.04) and with an increased risk of progression to advanced neoplasia (HR = 12; P = 0.03). Conclusion: In this study, p53 expression was found to be predictive of prevalent advanced neoplasia and progression to advanced neoplasia in patients with BE-IND.