title: A cross sectional study of p504s, CD133, and Twist expression in the esophageal metaplasia dysplasia adenocarcinoma sequence.
abstract: The incidence of esophageal adenocarcinoma has increased dramatically over recent years and Barrett's esophagus is considered the most established risk factor for its development. Endoscopic surveillance of Barrett's esophagus is therefore recommended but hinges on histological interpretation of randomly taken biopsies which is poorly reproducible. The use of biomarkers presents an opportunity to improve our ability to risk-stratify these patients.We examined three biomarkers namely p504s, CD133, and Twist in the setting of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma to evaluate differential expression between benign, dysplastic, and malignant Barrett's tissue in an exploratory cross-sectional study. Twenty-five cases each of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma were included along-with 25 cases of esophagectomy resections for Barrett's adenocarcinoma. The biomarkers were immunostained on automated Ventana(®) immunostainer. The biopsies were assessed for biomarker expression by two independent observers. Granular cytoplasmic staining of p504s was observed in dysplastic Barrett's biopsies and esophageal adenocarcinoma but not in Barrett's esophagus. Apical and membranous CD133 expression was also observed in dysplastic Barrett's and esophageal adenocarcinoma. Nuclear Twist expression was seen predominantly in stromal cells. There was increased p504s expression in dysplastic Barrett's esophagus and esophageal adenocarcinoma compared with controls. CD133 expression was detected for the first time in esophageal adenocarcinoma and dysplastic Barrett's esophagus. Twist expression was not convincing enough to be labeled as Barrett's biomarker. p504s and CD133 have the potential to differentiate benign from malignant Barrett's tissue in this exploratory study. Their validity should be established in prospective longitudinal studies.
authors.affiliation: Belfast Health and Social Care Trust, Queens University Belfast, Royal Victoria Hospital, Belfast, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ahmad
authors.forename: K
authors.initials: K
authors.lastname: Arthur
authors.forename: P
authors.initials: P
authors.lastname: Maxwell
authors.forename: A
authors.initials: A
authors.lastname: Kennedy
authors.forename: B T
authors.initials: BT
authors.lastname: Johnston
authors.forename: L
authors.initials: L
authors.lastname: Murray
authors.forename: D T
authors.initials: DT
authors.lastname: McManus
mesh_terms: D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D003430:Cross-Sectional Studies; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000473:pathology; D004947:Esophagus / Q000737:chemistry / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D010455:Peptides / Q000032:analysis*; D011230:Precancerous Conditions / Q000473:pathology; D019998:Racemases and Epimerases / Q000032:analysis*; D051879:Twist-Related Protein 1 / Q000032:analysis*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; D009687:Nuclear Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase
keywords: Barrett's esophagus; CD133; Twist; biomarker; esophageal adenocarcinoma; p504s