title: New molecular concepts of Barrett's esophagus: clinical implications and biomarkers.
abstract: Barrett's esophagus (BE) represents the most serious histological consequence of gastroesophageal reflux disease (GERD) that develops in 5-10% of patients with GERD. Given that BE is the only known precursor to esophageal adenocarcinoma (EA), a systematic endoscopic biopsy protocol can detect EAs at an early stage. However, endoscopic and histopathological evaluation of BE are not adequate for effective screening of high risk patients. Therefore, molecular abnormalities associated with BE have been considered as surrogate markers and their use as such is proposed. Flow cytometry is the most useful adjunct to histology, and ploidy status of BE is an independent risk factor. Cyclin D1 overexpression is inversely correlated with survival in EA. C-erbB2 (+) patients have poorer prognosis. High plasma adenomatous polyposis coli levels correlate with reduced patient survival. p53 expression allows patient risk for EA stratification. Nuclear factor-kappaB overexpression inversely correlates with good response to adjuvant chemotherapy and radiotherapy in EA. Patients with cyclooxygenase-2 overexpression have reduced survival rates. Increased E-cadherin staining is associated with shorter survival in EA patients who received chemoradiotherapy. Finally, existing data cannot rule out a correlation between EA and colorectal tumors. Seventeen BE molecular alterations yielded noteworthy clinical implications. Apart from endoscopy and histology, these data allow for better risk stratification for patients with BE and for more efficient and timely therapeutic approaches.
authors.affiliation: Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Kyrgidis
authors.forename: Jannis
authors.initials: J
authors.lastname: Kountouras
authors.forename: Christos
authors.initials: C
authors.lastname: Zavos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Chatzopoulos
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000209:etiology; D025601:Adenomatous Polyposis Coli Protein / Q000097:blood; D001471:Barrett Esophagus / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D015820:Cadherins / Q000378:metabolism; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000150:complications; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2; D016099:Endoscopy, Gastrointestinal; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000209:etiology; D005764:Gastroesophageal Reflux / Q000150:complications*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012307:Risk Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D015415:Biomarkers; D014408:Biomarkers, Tumor; D015820:Cadherins; D019938:Cyclin D1; D051546:Cyclooxygenase 2; D008565:Membrane Proteins; D016328:NF-kappa B; D011451:Prostaglandin-Endoperoxide Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C496540:PTGS2 protein, human