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CDX-2 Expression in Esophageal Biopsies Without Goblet Cell Intestinal Metaplasia May Be Predictive of Barrett’s Esophagus

  • James Saller
  • Sameer Al Diffalha
  • Kevin Neill
  • Rahill A. Bhaskar
  • Cecilia Oliveri
  • David Boulware
  • Henry Levine
  • Isaac Kalvaria
  • F. Scott Corbett
  • Arun Khazanchi
  • Jason Klapman
  • Domenico CoppolaEmail author
Original Article

Abstract

Background

CDX-2 is a nuclear homeobox transcription factor not normally expressed in esophageal and gastric epithelia, reported to highlight intestinal metaplasia (IM) in the esophagus. Pathological absence of goblet cells at initial screening via hematoxylin and eosin (HE) and alcian blue (AB) staining results in patient exclusion from surveillance programs.

Aims

This study aimed to determine whether non-goblet cell IM, as defined by CDX-2 positivity, can be considered to be a precursor to Barrett’s esophagus (BE).

Methods

This study received IRB approval (17,284). Patients with gastroesophageal reflux disease (n = 181) who underwent upper-gastrointestinal endoscopy with biopsies of the distal esophagus to rule out BE using HE/AB staining and CDX-2 immunostaining were followed for 3 years. Initial and follow-up staining results were evaluated for age/sex.

Results

Differences between development of goblet cell IM in CDX-2-negative and CDX-2-positive groups were evaluated. A Kaplan–Meier curve showed that, out of the 134 patients initially positive for CDX-2, 25 (18.7%) had developed goblet cell IM after 2 years and 106 (79.1%) after 3 years. Conversely, of the 47 patients initially negative for CDX-2, 8 (17.9%) developed goblet cell IM after 24 months and only 11 (23.8%) after 40 to 45 months (P = .049; age-adjusted Cox proportional hazard regression model).

Conclusion

In cases that are initially AB negative and CDX-2 positive, CDX-2 was demonstrated to have a potential prognostic utility for early detection of progression to BE. CDX-2 expression is significantly predictive for risk of goblet cell IM development 40 to 45 months after initial biopsy.

Keywords

Barrett’s esophagus Immunohistochemistry CDX-2 Dysplasia 

Abbreviations

AB

Alcian blue

BE

Barrett’s esophagus

EAC

Esophageal adenocarcinoma

GERD

Gastroesophageal reflux disease

HE

Hematoxylin and eosin

IM

Intestinal metaplasia

TF

Transcription factor

Notes

Acknowledgment

We thank Paul Fletcher and Daley Drucker (H. Lee Moffitt Cancer Center and Research Institution) for editorial assistance. They were not compensated for their assistance beyond their regular salaries. This work has been supported in part by the Tissue Core Facility at the H. Lee Moffitt Cancer Center and Research Institute: an NCI-designated Comprehensive Cancer Center (P30-CA076292).

Author’s contribution

JS, SAD, KN, RB, and CO collected material used for analyses and reviewed pathology reports and tabulated data; JS, SAD, and RB drafted the manuscript; SAD, KN, CO, and DC reviewed the HE slides and the AB/CDX-2 stains, confirming the pathological diagnoses; DB ran the biostatical analyses; HL, IK, FSC, JK, and AK reviewed the manuscript and provided clinical input and patient data; DC conceptualized the hypothesis and study design and finalized the manuscript.

Funding

This work has been supported in part by the Tissue Core Facility at the H. Lee Moffitt Cancer Center and Research Institute: an NCI-designated Comprehensive Cancer Center (P30-CA076292).

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • James Saller
    • 1
  • Sameer Al Diffalha
    • 1
  • Kevin Neill
    • 1
  • Rahill A. Bhaskar
    • 1
  • Cecilia Oliveri
    • 5
  • David Boulware
    • 2
  • Henry Levine
    • 5
  • Isaac Kalvaria
    • 6
  • F. Scott Corbett
    • 6
  • Arun Khazanchi
    • 6
  • Jason Klapman
    • 3
  • Domenico Coppola
    • 1
    • 4
    Email author
  1. 1.Departments of Anatomic PathologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  2. 2.BiostatisticsH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  3. 3.EndoscopyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  4. 4.Tumor BiologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  5. 5.Center For Digestive HealthOrlandoUSA
  6. 6.Florida Digestive Health SpecialistsLakewood RanchUSA

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