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Minichromosomal Maintenance Component Complex 5 (MCM5) as a Marker of Barrett’s Esophagus-Related Neoplasia: A Feasibility Study

  • M. Everson
  • C. Magee
  • D. Alzoubaidi
  • S. Brogden
  • D. Graham
  • L. B. Lovat
  • M. Novelli
  • R. HaidryEmail author
Original Article
  • 72 Downloads

Abstract

Background

The endoscopic detection of esophageal cancer is suboptimal in both patients referred with dyspeptic symptoms and those enrolled in Barrett’s surveillance programs. MCM5 expression in cells collected from gastric fluid may be correlated with the presence of dysplasia or adenocarcinoma. Analysis of this biomarker may improve the detection of cancer.

Methods

Sixty-one patients were enrolled at a single UK referral center. From each patient, 5–10 ml of gastric fluid was aspirated endoscopically. Patients were categorized according to their histology, normal, non-dysplastic Barrett’s (NDBE), high-grade dysplastic Barrett’s (HGD), and esophageal adenocarcinoma (EAC). All histology was confirmed by Seattle protocol biopsies or endoscopic mucosal resection. Samples were centrifuged, and the cell pellet was lysed. MCM5 expression levels were quantified using a proprietary immunoassay. The mean MCM5 expression was compared between groups by Kruskal–Wallis test. ROC curves were also used to assess diagnostic utility.

Results

The mean expression of MCM5 increases as patients progress from a normal esophagus to NDBE, HGD, and EAC (14.4; 49.8; 112.3; and 154.1, respectively). There was a significant difference in the MCM5 expression of patients with a normal esophagus compared to those with EAC (p = 0.04). There was a trend toward higher MCM5 expression in patients with EAC compared to those with NDBE (p = 0.34). MCM5 expression was a fair discriminator (AUC 0.70 [95% CI 0.57–0.83]) between patients without neoplasia (normal and NDBE) and those with early neoplasia (HGD and EAC).

Conclusion

MCM5 expression in gastric fluid samples can differentiate patients with a histologically normal esophagus compared to those with early adenocarcinoma. Larger, powered studies are needed to assess whether it can be used to differentiate those with HGD from NDBE.

Keywords

Barrett’s esophagus Esophageal cancer Endoscopy Biomarkers 

Notes

Funding

RJH has received research grant support from Pentax Medical, Cook Endoscopy, Fractyl ltd, C2 Therapeutics, and Medtronic plc to support research infrastructure. This was a commercially sponsored study by Arquer Diagnostics Ltd.

Author’s contribution

ME, DG, and RH helped in study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; and statistical analysis. CM, DA, SB, and LBL contributed to acquisition of data and critical revision of the manuscript for important intellectual content.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

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

Authors and Affiliations

  • M. Everson
    • 1
    • 2
  • C. Magee
    • 2
  • D. Alzoubaidi
    • 1
    • 2
  • S. Brogden
    • 2
  • D. Graham
    • 1
    • 2
  • L. B. Lovat
    • 1
    • 2
  • M. Novelli
    • 3
  • R. Haidry
    • 1
    • 2
    Email author
  1. 1.Division of Surgery and Interventional ScienceUniversity College LondonLondonUK
  2. 2.Department of GastroenterologyUniversity College Hospital NHS Foundation TrustLondonUK
  3. 3.Department of PathologyUniversity College Hospital NHS Foundation TrustLondonUK

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