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

Table 2 Summary of the biomarkers and the prognostic impact in esophageal adenocarcinoma

Category of cell alteration	Biomarker	Sample size (n)	Endpoint	Findings	Statistical significance	Ref.
Self sufficiency in growth signals	Cyclin D	124	Survival	2 of 3 genotypes confers a poorer overall survival	P = 0.0003	[77]
	EGFR	103	Survival	Expression showed a trend towards a correlation with poorer overall survival	P = 0.07	[78]
		75	Survival	Decreased expression correlated with poorer survival on univariate analysis only	P = 0.034	[79]
	Ki-67	59	Survival	Low levels (< 10%) of staining correlated with poorer survival	HR: 3.9, P = 0.02	[80]
	Her2/neu	63	Survival	Amplification detected by FISH correlated with poorer survival	P = 0.03	[81,82]
	TGF-α	61	Survival	Low levels significantly correlated with cancer specific death	P = 0.03	[83]
		87	Tumor progression, lymph node metastasis	High levels significantly correlated with:		[84]
				Tumor progression	P = 0.025
				Lymph node metastasis	P < 0.05
Insensitivity to growth inhibitory (antigrowth) signals	TGF-β1	123	Survival	Overexpression correlated with poorer survival on univariate analysis only	P = 0.0255	[85]
		57	Survival	High plasma levels correlated with poorer overall survival	P = 0.0317	[86]
	APC	52	Survival	High plasma levels of methylation of APC associated with poorer survival	P = 0.016	[87]
	P21	30	Survival	Alteration in expression after chemotherapy correlated with better survival	P = 0.011	[88,89]
Evasion of programmed cell death (apoptosis)	P53	30	Survival	Alteration in expression after chemotherapy correlated with better survival	P = 0.011	[88]
	Bcl-2	35	Survival	Expression correlated with poorer survival	P = 0.03	[90]
	COX-2	100	T-stage, N-stage, tumor recurrence and survival	Higher levels expression correlated with:		[91]
				Higher T-stage,	P = 0.008
				Higher N-stage,	P = 0.049
				Increased risk of tumor recurrence	P = 0.01
				Poor survival	P < 0.001
		20	Survival	Strong staining correlated with poorer survival	P = 0.03	[92]
		145	Distant metastasis, local recurrence and survival	Strong staining correlated with:		[93]
				Distant metastasis	P = 0.02
				Local recurrence	P = 0.05
				Poorer survival	P = 0.002
	NF-κB	43	Survival	Activated NF-κB predictive of:		[94]
				Poorer disease free survival	P = 0.010
				Poorer overall survival	P = 0.015
Limitless replicative potential	Telomerase	46	Survival	Higher telomere-length ratio shown to be an independent poor prognostic factor	P < 0.02	[95]
Sustained angiogenesis	CD105	75	Survival, angiolymphatic invasion, lymph node metastasis and tumor stage and distant metastasis	Significant correlation between expression and:		[96]
				Poorer survival	P < 0.01
				Presence of angiolymphatic invasion	P < 0.05
				More lymph node metastasis	P < 0.01
				Higher tumor stage	P < 0.001
				More distant metastasis	P < 0.01
	VEGF	75	Survival, angiolymphatic invasion, lymph node metastasis, stage of tumor and distant metastasis	Significant correlation between high expression and:		[96]
				Poorer survival	P < 0.01
				Presence of angiolymphatic invasion	P < 0.05
				More lymph node metastasis	P < 0.01
				Higher stage of tumor	P < 0.01
				More distant metastasis	P < 0.01
Tissue invasion and metastasis	Cadherin	59	Survival	Reduced level correlated with poorer overall survival	HR: 3.3, P = 0.05	[80]
	uPA	54	Survival	High uPA correlated with poorer survival	P = 0.0002	[97]
	TIMP	24	Survival and disease stage	Reduction of expression correlated with poorer overall survival and higher disease stage	P = 0.007	[98]
					P = 0.046
Others	Promoter hypermethylation	41	Survival and tumor recurrence	Earlier tumor recurrence and poorer overall survival if > 50% of gene profile methylated	P = 0.05	[99]
					P = 0.04
		84	Differentiation	Hypermethylation of MGMT (Methylated-DNA-protein-cysteine methyltransferase) gene correlated with:	P = 0.0079	[100]
				Higher tumor differentiation

EGFR: Epidermal growth factor receptor; Her2/neu: Human EGFR2; TGF: Transforming growth factor; APC: Adenomatosis polyposis coli; P21: Cyclin-dependent kinase inhibitor 1; Bcl-2: B-cell lymphoma 2; COX-2: Cyclooxygenase-2; NF-κB: Nuclear factor-κB; CD105: Endoglin; VEGF: Vascular endothelial growth factor; uPA: Urokinase-type plasminogen activator; TIMP: Tissue inhibitor of metalloproteinase.