title: p53 protein accumulation predicts malignant progression in Barrett's metaplasia: a prospective study of 275 patients.
abstract: OBJECTIVE
  The purpose of this study was to determine prospectively whether p53 protein accumulation in biopsies of Barrett's metaplasia (BM) is a predictor of malignant progression, without relying on dysplasia grading.
  
  
  RESULTS
  Sections of formalin-fixed paraffin-embedded tissue from the initial biopsies of 275 patients with BM, who had no high-grade dysplasia (HGD) or oesophageal adenocarcinoma (EAC), were stained for p53 by immunohistochemistry. The mean follow-up was 41 months. p53-positive biopsies were divided into four groups: scattered positive cells, multifocal scattered positive cells, aggregates of positive cells, and multifocal aggregates of positive cells. Kaplan-Meier analysis with the log-rank test was used to determine the rate of progression to HGD/EAC. Of the 275 patients, 227 had initial biopsies that were completely negative for p53, and, of these, one (0.4%) progressed to HGD/EAC; none of 24 (0%) patients with scattered positive cells and none of four (0%) of patients with multifocal scattered positive cells progressed. In contrast, five of 16 (31.25%) patients with aggregates of positive cells and three of four (75%) of those with multifocal aggregates of positive cells progressed to HGD/EAC. Kaplan-Meier analysis with log-rank statistics showed the difference in progression rate between the five groups to be highly significant (P < 0.0001).
  
  
  CONCLUSIONS
  We conclude that p53 protein accumulation, detected by immunohistochemistry in aggregates of cells, is a significant predictor of malignant progression in patients with BM.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, McGovern Medical School, and Memorial Hermann Hospital-TMC, Houston, TX, USA.
authors.forename: Mamoun
authors.identifier: http://orcid.org/0000-0001-9618-3451
authors.initials: M
authors.lastname: Younes
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Brown
authors.affiliation: Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Gregory Y
authors.initials: GY
authors.lastname: Lauwers
authors.affiliation: Section of Gastroenterology, Department of Medicine, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Gulchin
authors.initials: G
authors.lastname: Ergun
authors.affiliation: Section of Gastroenterology, Department of Medicine, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Meriano
authors.affiliation: Section of Gastroenterology, Department of Medicine, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: A Carl
authors.initials: AC
authors.lastname: Schmulen
authors.affiliation: Section of Gastroenterology, Department of Medicine, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Barroso
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Texas Health Science Center at Houston, McGovern Medical School, and Memorial Hermann Hospital-TMC, Houston, TX, USA.
authors.forename: Atilla
authors.initials: A
authors.lastname: Ertan
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000473:pathology; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Barrett's oesophagus; dysplasia; immunohistochemistry; oesophageal cancer