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, α-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.