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

Dig Dis Sci. 2019 Oct;64(10):2815-2822. doi: 10.1007/s10620-019-05607-5. Epub 2019 Apr 13.

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; Biomarkers; Endoscopy; Esophageal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / diagnosis
  • Adenocarcinoma* / metabolism
  • Adenocarcinoma* / pathology
  • Barrett Esophagus* / diagnosis
  • Barrett Esophagus* / metabolism
  • Barrett Esophagus* / pathology
  • Biomarkers / analysis
  • Biopsy / methods
  • Cell Cycle Proteins / analysis*
  • DNA Replication
  • Disease Progression
  • Early Detection of Cancer / methods
  • Endoscopy, Digestive System / methods
  • Esophageal Neoplasms* / diagnosis
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / pathology
  • Feasibility Studies
  • Female
  • Gastric Juice / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Precancerous Conditions* / diagnosis
  • Precancerous Conditions* / metabolism
  • Precancerous Conditions* / pathology

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • MCM5 protein, human

Supplementary concepts

  • Adenocarcinoma Of Esophagus