Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2016; 22(39): 8770-8778
Published online Oct 21, 2016. doi: 10.3748/wjg.v22.i39.8770
Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program
Hao Zhang, Hao Li, Qing Ma, Fang-Yan Yang, Tao-Yu Diao
Hao Zhang, Department of Gastroenterology, The Third Hospital of Jinan, Jinan 250132, Shandong Province, China
Hao Li, Tumor Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Qing Ma, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
Fang-Yan Yang, Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu 610041, Sichuan Province, China
Tao-Yu Diao, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, Shandong Province, China
Author contributions: Zhang H, Li H and Ma Q contributed equally to this study; Li H made a substantial contribution to conception and design; Zhang H, Ma Q, Yang FY and Diao TY performed the experiments and data analysis; and Li H interpreted the data.
Supported by the National Natural Science Foundation of China, No. 30571601.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Shandong Academy of Medical Sciences.
Informed consent statement: All participants gave their written informed consent.
Conflict-of-interest statement: There are no conflicts of interest to declare for all authors of the manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hao Li, MD, Vice Professor of Medicine, Tumor Center, Qilu Hospital of Shandong University, No. 107 Wenhuaxi Road, Jinan 250012, Shandong Province, China. haoli2003611@163.com
Telephone: +86-531-82169873 Fax: +86-531-82169873
Received: June 19, 2016
Peer-review started: June 20, 2016
First decision: July 29, 2016
Revised: August 23, 2016
Accepted: September 14, 2016
Article in press: September 14, 2016
Published online: October 21, 2016
Processing time: 123 Days and 6.4 Hours
Abstract
AIM

To determine the association of p53, carcinoembryonic antigen (CEA) and CA19-9 protein expression with esophageal carcinogenesis.

METHODS

An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia (BCH), 247 with low-grade dysplasia (LGD), 51 with high-grade dysplasia (HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROC curve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions.

RESULTS

The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH.

CONCLUSION

p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.

Keywords: Esophageal squamous cell cancer; Esophageal squamous cell dysplasia; p53; Carcinoembryonic antigen; CA19-9; Immunohistochemistry; Prediction

Core tip: Immunohistochemical detection of p53, carcinoembryonic antigen (CEA) and CA19-9 proteins was carried out in patients with basal cell hyperplasia, low-grade dysplasia, high-grade dysplasia, invasive cancer, and normal controls from an area with a high incidence of esophageal lesions. Our data suggest that p53, CEA, and CA19-9 protein expression correlated with the stages of esophageal carcinogenesis. In an endoscopic screening program, the expression of these three biomarkers will be a useful panel for identifying high-risk patients with precancerous lesions, and the results will provide a basis for targeted prevention in a high-incidence area of esophageal carcinoma.