BACKGROUND: The effectiveness of photodynamic therapy (PDT) for ablation of high grade dysplasia (HGD) in Barrett's esophagus (BE) is typically reported histologically. Following successful PDT, Barrett's mucosa is replaced with neosquamous mucosa. The objective of this study was to compare the expression of p53 protein in neosquamous mucosa as compared to that in HGD samples not treated with PDT. PATIENTS AND METHODS: The patients were divided into two groups. Group I patients (n = 12) had been treated with PDT for HGD and provided 23 biopsy samples of neosquamous mucosa. Group II patients (n = 10) had not received any ablative therapies for BE and provided 14 HGD samples. The immunohistochemical (IHC) staining for p53 protein was performed using mouse anti-human monoclonal antibody DO-1. The degree of p53 protein expression in the cell nuclei was scored using an established IHC scoring system (0 for negative samples and range of 2 to 8 for positive samples). RESULTS: The HGD samples showed diffuse strong p53 staining. The median IHC score for HGD was 7.0. The median IHC score for neosquamous mucosa following PDT was 4.0, with positive scores indicating weak staining in the basal layer of the neosquamous samples. There was significantly lower p53 expression in the neosquamous samples compared to that in the HGD samples (p < 0.001). CONCLUSION: Significantly lower p53 protein expression was detected in neosquamous mucosa of patients who had received PDT for HGD, suggesting a decreased risk for neoplastic progression after treatment.