title: Persistence of Human Papillomavirus, Overexpression of p53, and Outcomes of Patients After Endoscopic Ablation of Barrett's Esophagus.
abstract: We investigated the role of high-risk human papillomavirus (hr-HPV) in patients with Barrett's dysplasia and adenocarcinoma (EAC). Clearance vs persistence of HPV (DNA, E6 or E7 mRNA, and p16INK4A protein) and overexpression or mutation of p53 were determined for 40 patients who underwent endotherapy for Barrett's dysplasia or EAC. After ablation, dysplasia or neoplasia was eradicated in 34 subjects (24 squamous, 10 intestinal metaplasia). Six patients had detectable lesions after treatment; 2 were positive for transcriptionally active hr-HPV, and 4 had overexpression of p53. Before endotherapy, 15 patients had biologically active hr-HPV, 13 cleared the infection with treatment, and dysplasia or EAC was eliminated from 12 patients. One patient who cleared HPV after ablation acquired a p53 mutation, and their cancer progressed. Of 13 patients with overexpression of p53 before treatment, 10 cleared the p53 abnormality after ablation with eradication of dysplasia or neoplasia, whereas 3 of 13 had persistent p53 mutation-associated dysplasia after endotherapy (P = .004). Immunohistochemical and sequence analyses of p53 produced concordant results for 36 of 40 samples (90%). Detection of dysplasia or neoplasia after treatment was associated with HPV persistence or continued p53 overexpression.
authors.affiliation: Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales, Australia; South Western Sydney Clinical School, University of New South Wales, Kensington, Sydney, New South Wales, Australia; Department of Gastroenterology and Hepatology, Bankstown-Lidcombe Hospital, South Western Sydney Local Health Network, Bankstown, Sydney, New South Wales, Australia. Electronic address: Shan.Rajendra@sswahs.nsw.gov.au.
authors.forename: Shanmugarajah
authors.initials: S
authors.lastname: Rajendra
authors.affiliation: Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales, Australia; South Western Sydney Clinical School, University of New South Wales, Kensington, Sydney, New South Wales, Australia.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales, Australia; South Western Sydney Clinical School, University of New South Wales, Kensington, Sydney, New South Wales, Australia; Department of Gastroenterology and Hepatology, Bankstown-Lidcombe Hospital, South Western Sydney Local Health Network, Bankstown, Sydney, New South Wales, Australia.
authors.forename: Darren
authors.initials: D
authors.lastname: Pavey
authors.affiliation: Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center and University of Kansas City, Missouri.
authors.forename: Prateek
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Anatomical Pathology, South Western Sydney Area Pathology Service, Liverpool, Sydney, New South Wales, Australia.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Anatomical Pathology, South Western Sydney Area Pathology Service, Liverpool, Sydney, New South Wales, Australia; Discipline of Pathology, School of Medicine, University of Western Sydney, Sydney, New South Wales, Australia.
authors.forename: Cheok Soon
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology and Nutrition, Loyola University Medical Center, Maywood, Illinois.
authors.forename: Neil
authors.initials: N
authors.lastname: Gupta
authors.affiliation: School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia.
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Ball
authors.affiliation: Department of Gastroenterology and Hepatology, Bankstown-Lidcombe Hospital, South Western Sydney Local Health Network, Bankstown, Sydney, New South Wales, Australia.
authors.forename: Raghubinder Singh
authors.initials: RS
authors.lastname: Gill
authors.affiliation: Department of Anatomical Pathology, South Western Sydney Area Pathology Service, Liverpool, Sydney, New South Wales, Australia.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wu
mesh_terms: D055011:Ablation Techniques / Q000379:methods*; D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery* / Q000821:virology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000473:pathology / Q000601:surgery* / Q000821:virology; D004724:Endoscopy / Q000379:methods*; D004938:Esophageal Neoplasms / Q000473:pathology / Q000601:surgery* / Q000821:virology; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Barrett’s Esophagus; Carcinogenesis; Genetic; Immunohistochemistry; Tumor Suppressor