Predictors of progression in Barrett's esophagus: current knowledge and future directions

Abstract

Barrett's esophagus (BE) is the strongest risk factor for esophageal adenocarcinoma (EAC), a malignancy with persistently poor long-term outcomes. EAC is thought to develop through progression of metaplasia to dysplasia to invasive carcinoma. Identification of factors predicting progression to EAC would help in focusing surveillance, chemoprevention, or ablation for those deemed to be at highest risk of progression. We performed a comprehensive review of the literature and summarized current evidence on risk factors for progression in subjects with known BE. Clinical and demographic factors (age, male gender, length of BE segment) are associated with modestly increased odds of progression to EAC in some studies. Biomarkers such as aneuploidy and p53 loss of heterozygosity have been associated with increased risk of progression to high-grade dysplasia and/or EAC in single-center prospective cohort studies. Promising newer techniques and markers have been recently reported with the potential to help risk stratify BE subjects. Development of a comprehensive BE risk progression score comprised of both clinical and biomarker variables should be the ultimate goal and can be achieved by multicenter prospective collaborative efforts. Although it would be challenging, creation of such a score has the potential to improve outcomes and make the management of patients with BE more cost-effective.

Figure 1

Automated cytokeratin-assisted laser scanning cytometry for calculations of aneuploidy. Representative images of DAPI staining for nuclei (a), cytokeratin staining to identify epithelial cells (b) and overlay of the two (c) (×20 magnification). The histograms show results of these calculations from sections with intestinal metaplasia (d) and high-grade dysplasia (e). More DAPI fluorescence indicates more DNA content. Note the shorter 2N (diploid) peak in (e) compared with (d) that suggests a higher number of cells with > 2N DNA content, hence aneuploidy. The red line in e indicates extreme aneuploidy (> 5N). The second smaller peak in d shows normal 4N (tetraploid) fraction that represents the normal doubling of chromosomes in the S phase of cell cycle.