Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2015; 21(9): 2770-2776
Published online Mar 7, 2015. doi: 10.3748/wjg.v21.i9.2770
CDX2 protein expression compared to alcian blue staining in the evaluation of esophageal intestinal metaplasia
Dennis R Johnson, Maisoun Abdelbaqui, Maryam Tahmasbi, Zoltan Mayer, Hung-Wei Lee, Mokenge P Malafa, Domenico Coppola
Dennis R Johnson, Maisoun Abdelbaqui, Maryam Tahmasbi, Domenico Coppola, Department of Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
Zoltan Mayer, Hung-Wei Lee, Florida Digestive Health Specialists, Lakewood Ranch, FL 34202, United States
Mokenge P Malafa, Domenico Coppola, Department of Oncological Sciences, University of South Florida, Tampa, FL 33612, United States
Mokenge P Malafa, GI Tumor Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
Domenico Coppola, Tumor Biology Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
Author contributions: Abdelbaqui M and Tahmasbi M performed the experiments; Johnson DR reviewed the results and drafted the manuscript; Mayer Z and Lee HW co-ordinated and provided the collection of part of the human material; Malafa MP and Coppola D reviewed the data and finalized the manuscript; and Coppola D designed the research.
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: Domenico Coppola, MD, Department of Anatomic Pathology, Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., MCC-PATH, Tampa, FL 33612, United States. domenico.coppola@moffitt.org
Telephone: +813-745-3275 Fax: +813-449-8323
Received: July 18, 2014
Peer-review started: July 18, 2014
First decision: September 15, 2014
Revised: October 16, 2014
Accepted: November 7, 2014
Article in press: November 11, 2014
Published online: March 7, 2015
Processing time: 234 Days and 10 Hours
Abstract

AIM: To compare the sensitivity and specificity of CDX2 and alcian blue (AB) pH 2.5 staining in identifying esophageal intestinal metaplasia.

METHODS: One hundred and ninty-nine biopsies from 186 patients were retrospectively reviewed and categorized as Barrett’s esophagus (BE) (n = 108); non-Barrett’s esophagus (NBE) (n = 48); columnar blue cells (CB) and esophageal glands (EG) (n = 43). The biopsies were stained with AB and immunostained for CDX2 using a mouse monoclonal antibody from Biogenex (clone CDX2-88) and the Ventana Discovery X automated immunostainer. The positive and negative predictive value of each group was used to determine the predictive power of CDX2 and AB in diagnosing intestinal metaplasia.

RESULTS: All of the 108 BE biopsies (100%) were positive for AB and 102 of them (94.4%) were positive for CDX2. The six BE patients (5.6%) who failed to stain with CDX2 were found to have lost the focus of intestinal metaplasia upon deeper sectioning for immunostaining. Both AB and CDX2 were negative in 43 out of 48 (89.6%) NBE cases. Five NBE patients (10.4%) were falsely positive for AB due to the presence of EG and CB in these biopsies. These cases were all CDX2 negative. In addition, 5 AB negative NBE were found to be CDX2 positive. Based on these results the CDX2 immunostain had similar sensitivity but higher specificity (100% vs about 91%) than AB in detecting intestinal type metaplasia in these samples. Our data shows that CDX2 has a better PPV in detecting intestinal metaplasia as compared to AB (95.6% vs 71.5%, respectively).

CONCLUSION: CDX2 has a better positive predictive value than AB in detecting intestinal metaplasia. CDX2 may be useful when challenged by gastro-esophageal biopsies containing mimikers of BE.

Keywords: Barrett’s esophagus; Alcian blue pH 2.5; CDX2; Intestinal metaplasia; Esophageal glands; Columnar blue cell

Core tip: Our data show that the use of CDX2 immunostain in biopsies performed to rule out esophageal intestinal metaplasia (Barrett esophagus) has the advantage of discriminating between Barrett’s esophagus and esophageal glands. The latter is typically strongly positive for alcian blue (AB) pH 2.5 but negative for CDX2. CDX2 also discriminates between BE and columnar blue cells which are also positive for AB. Our data shows that CDX2 has a better positive predictive value in detecting intestinal metaplasia as compared to AB (95.6% vs 71.5% respectively). These results support the utility of CDX2 stain in the correct diagnosis of Barrett esophagus.