Predictive biomarkers for Barrett's esophagus: so near and yet so far

Abstract

Barrett's esophagus (BE) is the strongest risk factor for the development of esophageal adenocarcinoma. However, the risk of cancer progression is difficult to ascertain in individuals, as a significant number of patients with BE do not necessarily progress to esophageal adenocarcinoma. There are several issues with the current strategy of using dysplasia as a marker of disease progression. It is subject to sampling error during biopsy acquisition and interobserver variability among gastrointestinal pathologists. Ideal biomarkers with high sensitivity and specificity are needed to accurately detect high-risk BE patients for early intervention and appropriate cost-effective surveillance. To date, there are no available molecular tests in routine clinical practice despite known genetic and epigenetic aberrations in the Barrett's epithelium. In this review, we present potential biomarkers for the prediction of malignant progression in BE. These include markers of genomic instability, tumor suppressor loci abnormalities, epigenetic changes, proliferation markers, cell cycle predictors, and immunohistochemical markers. Further work in translating biomarkers for routine clinical use may eventually lead to accurate risk stratification.

Keywords: Barrett's esophagus; biomarker; early detection of cancer; esophageal adenocarcinoma; fluorescence in situ hybridization.

Fig. 1

Number of published articles on biomarkers in Barrett’s esophagus from 1980 to 2011.

Fig. 2

Fluorescence in situ hybridization (FISH) with representative cytology samples. Representative sample of brush cytology specimen after FISH with probes for 8q24 (MYC) (aqua), 9p21 (p16) (red), 17q11.2 (ERBB2) (green), and 20q13.2 (ZNF217) (gold). The normal cell has two signals from each of the four probes. The abnormal cell was found to have gain of multiple probes.