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.
Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Barrett’s Esophagus; Carcinogenesis; Genetic; Immunohistochemistry; Tumor Suppressor
Comment in
- Does Human Papillomavirus Cause Esophageal Adenocarcinoma? [Clin Gastroenterol Hepatol. 2015]
Authors:
Rajendra S, Wang B, Pavey D, Sharma P, Yang T, Lee CS, Gupta N, Ball MJ, Gill RS, Wu X.
Clin Gastroenterol Hepatol. 2015 Jul;13(7):1364-1368.e5. doi: 10.1016/j.cgh.2014.11.017. Epub 2014 Nov 21.
Published: //www.ncbi.nlm.nih.gov/pubmed/25460562