Table 2.
Biomarker | Method | Remarks | Ref. | |
Diagnostic | TFF3 | IHC | To screen asymptomatic patients for BE | [49,50] |
Chromosome 7 and 17 changes | IDKA and FISH | Early stages of BE | [52] | |
8q24 (C-MYC), 17q12 (HER2), and 20q13 changes | FISH | Early stages of BE | [53] | |
17q11.2 (ERBB2) | Microarray analysis | EAC | [54] | |
Serum proteomic analysis | Mass spectrometry | EAC | [55] | |
Predictive | P16 allelic loss | FISH | Response to therapy | [56] |
DNA ploidy abnormalities | ICDA | Covariate value for recurrence | [57] | |
HSP27 | IHC | No response to therapy | [58] | |
Ephrin B receptor | Microarray | Response to therapy in EAC | [59] | |
Genetic polymorphism | qRT-PCR | Associated with clinical outcome | [60] | |
P21 | IHC | Correlated with better CTX response | [61] | |
P53 | IHC | Correlated with better CTX response | [62] | |
Progression markers | ERCC1 | IHC | Predicts CTX resistance | [16] |
P53 | IHC | Limited efficacy as a progression marker | [13,63] | |
DNA abnormalities | Flow cytometry | High risk for progression to EAC | [13] | |
LOH of 157p and 9p | Flow cytometry | Predict progression to EAC | [14] | |
EGFR | IHC | Overexpression in HGD and EAC | [64] | |
Cyclin A | IHC | Predicts progression to dysplasia | [65] | |
Cyclin D1 | IHC | Risk of Progression to EAC | [19] | |
Hypermethylation of p16, RUNX2,HPP1 | RT-PCR | Risk of progression to EAC/HGD | [22] | |
8 gene methylation panel | RT-PCR | Predicts progression to EAC/HGD | [66] | |
Prognostic biomarkers | Cathepsin D,AKR1D10,AKR1C2 mRNA levels | Western blot, qRt-PCR | Dysregulation predicts progression to EAC/HGD | [67] |
DCK, PAPSS2, SIRT,TRIM44 | RT-PCR, IHC | 4 gene signature in EAC , predict 5 year survival | [56] | |
P16 loss, C-MYC gain | FISH | Associated with therapy response | [68] | |
ASS expression | Microarray | Low expression associated with metastases | [69] | |
MicroRNA expression profile | Microarray, RT-PCR | Low level associated with worse prognosis in EAC | [70] | |
Cyclin D1 | IHC, FISH | Decreased survival | [71] | |
EGFR | IHC | Decreased expression associated with decreased survival | [72] | |
TGF-α | IHC, ISH | High level indicates progression and metastases | [73] | |
TGF-β1 | RT-PCR, ELISA | High expression associated with decreased survival | [73] | |
APC | PCR | High level associated with decreased survival | [74] | |
COX-2 | IHC | Associated with metastases and recurrence | [75] | |
Telomerase | Southern-blot and PCR | Associated with decreased survival | [76] | |
VEGF | IHC | Associated with metastases and decreased survival | [77] | |
Cadherin | IHC | Decreased level associated with decreased survival | [78] | |
TIMP | IHC, PCR | Decreased level associated with decreased survival | [79] |
ACIS: Automated cellular imaging system; ASS: Argininosuccinate synthase; APC: Adenomatous polyposis coli; BE: Barrett’s esophagus; COX: Cyclooxygenase; DCK: Deoxycytidine kinase; DICM: Digital image cytometry; EAC: Esophageal adenocarcinoma; EGFR: Epidermal growth factor receptor; ELISA: Enzymelinked immunosorbent assay; FISH: Fluorescence in-situ-hybridization; ICDA: Image cytometric DNA analysis; HSP27: Heat-shock protein 27; IHC: Immunohistochemistry; LOH: Loss of heterozygosity; PAPSS2: 3'-phosphoadenosine 5'-phosphosulfate synthase 2; PCR: Polymerase chain reaction; qRT: Quantitative reverse transcriptase; MLPA: Multiplex ligation dependent probe amplification; NF-κB: Nuclear factor kappa B; SIRT2: Sirtuin 2; SNP: Single nucleotide polymorphism; TFF3: Trefoil factor 3; TGF: Transforming growth factor; TIMP: Tissue inhibitors of metalloproteinases; TRIM44: Tripartite motifcontaining 44; uPA: Urokinase-type plasminogen activator; VEGF: Vascular endothelial growth factor.