Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma

Michelle A.C Reed,Rishi Singhal,Christian Ludwig,John B Carrigan,Douglas G Ward,Phillipe Taniere,Derek Alderson,Ulrich L Günther

doi:10.1016/j.neo.2016.11.003

Michelle A.C Reed, Rishi Singhal + Show 6 more

Open Access

https://doi.org/10.1016/j.neo.2016.11.003

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Journal: Neoplasia	Publication Date: Jan 31, 2017
Citations: 11	License type: cc-by

Affiliation: University of Birmingham

Abstract

Patients with Barrett's esophagus (BO) are at increased risk of developing esophageal adenocarcinoma (EAC). Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using 1H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO. The study included 46 patients with EAC, 7 patients with BO, and 68 controls who underwent endoscopy for dyspeptic symptoms with normal appearances. Within the cancer cohort, 9 patients had nonneoplastic Barrett's adjacent to the cancer suitable for biopsy. It was possible to distinguish between histologically normal, BO, and EAC tissue in EAC patients [area under the receiver operator curve (AUROC) 1.00, 0.86, and 0.91] and between histologically benign BO in the presence and absence of EAC (AUROC 0.79). In both these cases, sample numbers limited the power of the models. Comparison of histologically normal tissue proximal to EAC versus that from controls (AUROC 1.00) suggests a strong field effect which may develop prior to overt EAC and hence be useful for identifying patients at high risk of developing EAC. Excellent sensitivity and specificity were found for this model to distinguish histologically normal squamous esophageal mucosa in EAC patients and healthy controls, with 8 metabolites being very significantly altered. This may have potential diagnostic value if a molecular signature can detect tissue from which neoplasms subsequently arise.

Highlights

In many Western countries, rates of esophageal adenocarcinoma (EAC) have been increasing for more than 20 years, among overweight, white men and those with severe gastroesophageal reflux disease [1,2]
Tissue Samples Tissue samples were obtained from patients with EAC, patients with Barrett's esophagus (BO), and controls who presented to University Hospitals, Birmingham, UK, between May 2009 and March 2010
There are a few reports for metabolomics studies in esophageal squamous cell carcinoma [23,24], only two groups have analyzed tissue samples from EAC patients [16], with one study focused on the squamous mucosa of these patients [12]

Summary

Introduction

In many Western countries, rates of esophageal adenocarcinoma (EAC) have been increasing for more than 20 years, among overweight, white men and those with severe gastroesophageal reflux disease [1,2]. Among patients with gastroesophageal reflux disease, some develop Barrett's esophagus (BO), characterized by metaplastic columnar epithelium in which mucus-secreting goblet cells appear. In some patients, this lining becomes unstable, progressing from low-grade to high-grade dysplasia (HGD) and neoplasia. This lining becomes unstable, progressing from low-grade to high-grade dysplasia (HGD) and neoplasia Identification of this at-risk population presently relies on endoscopic surveillance of large cohorts of patients with BO, most of whom will not develop a cancer. The exact risk of patients with BO and HGD developing EAC is not known, but one meta-analysis gave a weighted incidence rate of 6.58 per 100 patient-years during the first 1.5 to 7 years [3].

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