The use of imaging and biomarkers in diagnosing Barrett’s esophagus and predicting the risk of neoplastic progression

Abstract

Long-standing gastroesophageal reflux disease can result in transformation of the normal squamous lining of the esophagus into columnar epithelium (with goblet cells). This condition, Barrett’s esophagus (BE), is considered a risk factor for esophageal cancer (EAC) and may be the cause of the increased incidence of EAC over the last few decades. Currently, endoscopy with biopsies revealing dysplasia is the best predictor for neoplastic progression in patients with BE. However, the use of more sophisticated imaging techniques and biomarkers with or without histological assessment may be helpful in more accurate prediction of malignant transformation in these patients. New approaches to the evaluation of BE such as epigenetics, miRNA analysis, detection of DNA content abnormalities and loss of heterozygosity have great potential to shed light on the complex gastroesophageal reflux disease –BE–EAC sequence.

Keywords::

• Barrett’s esophagus
• biomarkers
• DNA content abnormalities
• dysplasia
• endoscopy
• epigenetics
• esophageal adenocarcinoma
• imaging
• LOH
• miRNA

Acknowledgement

The authors would like to thank Stuart Spechler for his expert review and thoughtful suggestions in improving the manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The incidence of esophageal cancer is rising rapidly probably due to epidemic of obesity in western countries, contributing to increased prevalence of gastroesophageal reflux disease.

• The current gold standard for screening and diagnosis is four-quadrant mucosal biopsies performed every 1–2 cm to look for dysplasia. Limitations of this approach include false-negative sampling, interobserver variability in diagnosing dysplasia and invasive nature of testing.

• A variety of novel imaging modalities has been developed to improve visualization of the dysplastic epithelium and provide targeted biopsies in a bid to increase the overall diagnostic yield.

• There has been a great surge in research into biomarkers, yet clinical applicability is mostly limited by lack of data from prospective trials as well as technical difficulties.

• The use of p53 immunostaining as a clinical adjunct in diagnosing Barrett’s esophagus is becoming more popular due to its statistical robustness and ease of applicability.

• miRNAs, particularly salivary miRNAs, seem very promising for the development of a noninvasive screening and diagnostic modality. However, much more research is needed before it can be translated into a clinical setting.

• The future will likely be a combination of prediction models for at-risk patients, novel endoscopic techniques that can accurately localize dysplastic areas and provide adequate pathological samples that can be analyzed using multibiomarker panels.

Notes