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

Abstract

Background and Aim: 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

CDX2, COX2 and MUC2 Expressions in Barrett's Esophagus: Can They Be Useful in Determination of the Dysplasia?

“…Song et al showed that unconjugated dihydroxy bile acids were potent stimulators of COX2 induction in BE and EA cells (15). Similarly, several studies concluded that the increase in C0X2 results in increased cell proliferation, IM, dysplasia and EA (13,14). Besides these, Möbius et al have found increased COX2 expression in relation with increased Ki-67 score, increased neovascularization and decreased survival in EA patient (21).…”

“…COXl is constitutively expressed in most tissues and C0X2 is induced in response to inflammation (7). C0X2 is not expressed in non-infiamed gastrointestinal epithelium but is expressed in esophagitis, BE and intestinal metaplasia of the stomach and increases in the spectrum from metaplasia to cancer (7,13,14). Studies show that un-conjugated dihydroxy bile acids, chemodeoxycholic acid and deoxycholic acid are potent stimulators of COX2 induction in BE and EA cells (7,15), and increase in C0X2 results in increased cell proliferation, IM, dysplasia and EA (7).…”

Field defects in progression to gastrointestinal tract cancers

“…The normal appearing squamous epithelium of the esophagus of patients with BE and BEassociated adenocarcinoma has numerous alterations in gene expression compared to squamous epithelium of normal individuals without metaplasia or neoplasia [22]. These findings indicate that BE metaplasia may arise in a pre-existing field defect of the squamous epithelium.…”

Barrett’s to Oesophageal Cancer Sequence: A Model of Inflammatory-Driven Upper Gastrointestinal Cancer

“…Secreted protein acidic and rich in cysteine (SPARC) is a protein with multiple effects, including counteradhesive and antiproliferative functions, as well as cell cycle modulation and matrix remodelling properties [43]. SPARC is increased in BO and OAC [44], while its expression is higher in the normal oesophagus of Barrett's and cancer patients compared with healthy patients, suggesting that this may be a field effect in the oesophagus [45,46]. SPARC may be overexpressed in the tumour microenvironment in an attempt to inhibit tumour growth, while tumour cells themselves reduce SPARC.…”