The molecular signature of normal squamous esophageal epithelium identifies the presence of a field effect and can discriminate between patients with Barrett's esophagus and patients with Barrett's-associated adenocarcinoma.
OBJECTIVE
Genetic alterations in the normal tissues surrounding various cancers have been described, but a comprehensive analysis of this carcinogenic field effect in Barrett's-associated adenocarcinoma of the esophagus disease has not been reported. The aim of this study was to analyze the gene expression profile of a panel of highly selected genes in the normal squamous esophagus epihelium of patients with Barrett's esophagus, patients with Barrett's-associated adenocarcinoma, and a healthy control group to define the existence of a carcinogenic field effect, and to investigate the clinical importance of such a field effect in the management of Barrett's disease.


METHODS
Forty-nine histologic normal squamous esophageal epithelia collected from 19 patients with Barrett's esophagus, 20 patients with Barrett's-associated esophageal adenocarcinoma, and a healthy control group of 10 patients were studied. A quantitative real-time reverse transcription-PCR method (TaqMan) was used to measure the expression of a panel of genes with known associations with gastrointestinal carcinogenesis.


RESULTS
A widespread carcinogenic field effect was detected for more than 50% of the genes analyzed including Bax, BFT, CDX2, COX2, DAPK, DNMT1, GSTP1, RARalpha, RARgamma, RXRalpha, RXRbeta, SPARC, TSPAN, and VEGF. Based on the expression signature of the normal appearing squamous esophagus, a linear discriminant analysis was able to distinguish between the three groups of patients with an error rate of 0%.


CONCLUSIONS
This study provides the first comprehensive investigation of a carcinogenic field effect in Barrett's esophagus disease. Based on the gene expression signature of the normal esophagus, patients could be correctly characterized according to their pathologic classification by applying a linear discriminant analysis. Our results provide evidence that a molecular classification might have clinical importance for the diagnosis and treatment of patients with Barrett's esophagus disease.
Brabender
Jan
J
Department of Visceral and Vascular Surgery, University of Cologne, Germany. jan.brabender@t-online.de
Marjoram
Paul
P
Lord
Reginald V N
RV
Metzger
Ralf
R
Salonga
Dennis
D
Vallböhmer
Daniel
D
Schäfer
Hartmut
H
Danenberg
Kathleen D
KD
Danenberg
Peter V
PV
Selaru
Florin M
FM
Baldus
Stefan E
SE
Hölscher
Arnulf H
AH
Meltzer
Stephen J
SJ
Schneider
Paul M
PM
D000230:Adenocarcinoma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D003937:Diagnosis, Differential; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005819:Genetic Markers