Molecular biomarkers of progression from Barrett’s esophagus to esophageal adenocarcinoma

• Published in: Frontiers in gastroenterology (Lausanne, Switzerland) Vol. 2
• Main Authors: Taylor, Luke, Alastal, Hani Naeem, Rasheed, Ashraf
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 25.05.2023
• Subjects: Barrett’s oesophagus; biomarker; cyclin D1; dysplasia; oesophageal adenocarcinoma; β-catenin
• ISSN: 2813-1169; 2813-1169
• DOI: 10.3389/fgstr.2023.1007456

Introduction Barrett’s esophagus (BO) is a pre-malignant condition for esophageal adenocarcinoma (OAC), the incidence rate of which has risen dramatically over the last four decades in the Western world. The 5-year survival rate of OAC is poor, and one of the ways to improve it would be by focusing on identifying high-risk Barrett’s patients through a surveillance program. Currently, histologic dysplasia is the only recognized marker of progression to OAC. Molecular biomarkers found in tissue samples that predict which patients have a higher risk of progression to OAC may act as a reliable tool for the stratification of patients with BO. Aim To determine whether molecular biomarkers have a potential use in predicting which patients with BO have a higher risk of progression to OAC. Methods Immunohistochemistry was performed on 25 tissue samples obtained from the endoscopic biopsies of 19 patients with confirmed BO. Hematoxylin and eosin (H&E) staining was used to confirm the presence of BO and dysplasia. Staining was performed in an external independent laboratory. Statistical analysis using the Mann–Whitney U test was performed using R Studio ® statistical software. Results Of the 19 patients sampled, three had low-grade dysplasia (LGD), and all had confirmed metaplasia diagnostic of BO. Expression of cyclin D1 was noted to be elevated in patients with LGD compared with those with metaplasia only ( p = 0.042). Expression of Sox2 was elevated in metaplastic BO cells compared with normal squamous cells within the same stain (p = 0.046). Of all eight biomarkers tested, β-catenin had the greatest overall expression (p < 0.004). Conclusions Isolating elevated cyclin D1 in patients with LGD highlights its potential use as a biomarker in identifying BO patients at risk of developing dysplasia, and, in turn, their possible progression to OAC. Elevated levels of both Sox2 and β-catenin may also serve as markers for disease progression when overexpressed in BO patients. Both conclusions, however, would need long-term follow-up to fully establish their prognostic usefulness, as at the time of writing no patients in this study had gone on to develop OAC. Although only a small sample size was present for this study, and follow-up was limited, it serves as a strong pilot for further research into the use of novel biomarkers in predicting which BO patients are at high risk of developing dysplasia and progressing to OAC.