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

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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.

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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

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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).

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).

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Author notes

  1. James Saller and Sameer Al Diffalha are co-first authors.

Authors and Affiliations

  1. Departments of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    James Saller, Sameer Al Diffalha, Kevin Neill, Rahill A. Bhaskar & Domenico Coppola

  2. Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    David Boulware

  3. Endoscopy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Jason Klapman

  4. Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA

    Domenico Coppola

  5. Center For Digestive Health, Orlando, FL, USA

    Cecilia Oliveri & Henry Levine

  6. Florida Digestive Health Specialists, Lakewood Ranch, FL, USA

    Isaac Kalvaria, F. Scott Corbett & Arun Khazanchi

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Contributions

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.

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Correspondence to Domenico Coppola.

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Saller, J., Al Diffalha, S., Neill, K. et al. CDX-2 Expression in Esophageal Biopsies Without Goblet Cell Intestinal Metaplasia May Be Predictive of Barrett’s Esophagus. Dig Dis Sci 65, 1992–1998 (2020). https://doi.org/10.1007/s10620-019-05914-x

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