Aberrant p53 expression, a stronger risk factor for neoplastic progression in Barrett’s esophagus than confirmed low grade dysplasia: a large multicenter prospective cohort study

Background: Low grade dysplasia (LGD) diagnosed on multiple occasions is considered the strongest risk factor for neoplastic progression in patients with Barrett’s esophagus (BE); however, recent studies have shown that aberrant p53 expression may be a more powerful risk factor for progression. This study aimed to compare the association between aberrant p53 expression versus LGD diagnosed on two or more occasions and neoplastic progression risk. Methods: Patients with a BE segment length ≥ 2 cm were included in a multicenter prospective cohort. p53 expression was determined by immunohistochemistry staining. Neoplastic progression was defined as development of high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Multivariable Cox regression analyses were used to determine the association between selected variables and neoplastic progression risk. Results: 960 patients (median age 62; 73 % men) were included. During a median (interquartile range) follow-up of 6.3 (3.5–11.9) years, 81 patients (8 %) developed HGD/EAC. p53 expression was aberrant in 24 % of patients, and was strongly associated with an increased risk of progression (hazard ratio [HR] 20.0, 95 %CI 10.0–40.0). In contrast, LGD on multiple occasions was not similarly associated (HR 0.84, 95 %CI 0.47–1.53), after adjustment for age, sex, and segment length. Progression-free survival was better in patients with normal versus aberrant p53 expression, regardless of the histopathological diagnosis (P < 0.001). Conclusions: Aberrant p53 expression is strongly associated with an increased neoplastic progression risk in BE patients, regardless of the histopathological findings. It may therefore be a better parameter than confirmed LGD on multiple occasions to identify patients who might benefit from ablation therapy.