Biomarkers in Barrett’s esophagus and esophageal adenocarcinoma: Predictors of progression and prognosis

Table 1 Summary of the most promising biomarkers for identifying patients with Barrett’s esophagus at high risk of developing esophageal adenocarcinoma

Surveillance biomarker	Highest EDRN stage	Study size (n)1	Findings	Statistical significance	Ref.
HGD	4	15	Progression to EA in 4 out of 15 patients with unifocal HGD	RR not available	[29]
		485	20 patients with HGD treated with omeprazole only developed EA	RR not available	[30]
		327	33 out of 76 patients with HGD developed EA	RR 28 (95% CI: 13-63)	[31]
		1099	12 out of 75 patients with HGD developed EA	RR 12.1 (95% CI: 5-29.4)	[32]
Aneuploidy and LOH (Reid Panel)	4	243	Panel of biomarkers (LOH of 17p and 9p and DNA abnormalities) can best predict progression to EA	RR 38.7 (95% CI: 10.8-138.5)	[33]
			LOH of 17p alone	RR 10.6 (95% CI: 5.2-21.3)
			LOH of 9p alone	RR 2.6 (95% CI: 1.1- 6.0)
			Aneuploidy alone	RR 8.5 (95% CI: 4.3-17.0)
			Tetraploidy alone	RR 8.8 (95% CI: 4.3-17.7)
p53 positivity by immunohistochemistry	3	164	Diffuse or intense TP53 staining elevated in patients who developed EA compared to controls	OR 11.7 (95% CI: 1.93-71.4)	[34]
		48	3 out of 5 patients with low grade dysplasia who progressed to high grade dysplasia had positive p53	RR not available	[35]
Mcm2	3	27	Ectopic luminal surface expression predictive of progression to HGD or EA	OR 136 (95% CI: 7.5-2464)	[36]
Cyclin A	3	48	Ectopic luminal surface expression predictive of progression to HGD or EA	OR 7.6 (95% CI: 1.6-37)	[37]
Methylation markers	3	53	Hypermethylation of p16 (cyclin-dependent kinase inhibitor 2A), RUNX3 (Runt-related transcription factor 3) and HPP1 (transmembrane protein with EGF-like and two follistatin-like domain 2) associated with an increased risk of progression to high grade dysplasia or EA	OR 1.74 (95% CI: 1.33-2.2), 1.80 (95% CI: 1.08-2.81) and 1.77 (95% CI: 1.06-2.81), respectively	[38]
		195	A 8 gene methylation panel in combination with age could predict half of progressors to HGD or EA who would not have been diagnosed without the use of the panel	RR not available	[39]

¹Study size includes all patients in study and findings are extracted when relevant. Mcm2: Minichromosome maintenance protein 2; EA: Esophageal adenocarcinoma; HGD: High-grade dysplasia; LOH: Loss of heterozygosity; EDRN: Early Detection Research Network; RR: Relative risk; OR: Odds ratio; CI: Confidence interval.