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Abstract
The variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectiveness of surveillance programs in esophageal cancer. Based on the "field cancerization" hypothesis that tumors arise within a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling could differentiate between histologically normal tissue from individuals with and without esophageal cancer. Thirty-five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. Using 1H magic angle spinning-nuclear magnetic resonance spectroscopy of intact tissue, we generated metabolic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), and proximal histologically normal mucosa from a control group. Using multivariate regression and receiver-operator characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically normal tissues from cancer patients and from that of controls. Whereas 26% and 12% of the spectral profile regions were uniquely discriminating tumor or control tissue, respectively, 5% of the profile exhibited a significant progressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned to phosphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing compounds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence of esophageal cancer (n=123; area under the curve, 0.84; P<0.001). In conclusion, our findings support the hypothesis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. This indicates that metabolic profiling of tissue can potentially play a role in the surveillance of cancer by reporting on the phenotypic consequences of field cancerization.
Highlights
Esophageal cancer accounts for 6% of all cancer deaths worldwide [1]
Based on the concept of field cancerization, we examined the hypothesis that metabolic differences between histologically normal mucosa from esophageal cancer patients and from nondiseased controls would be detected by MASNMR analysis and aimed to identify putative biomarkers of potential value in clinical applications
Histopathologic examination after H&E staining and immunohistochemistry confirmed the presence of adenocarcinoma in all tumor tissue samples (Fig. 1B)
Summary
Esophageal cancer accounts for 6% of all cancer deaths worldwide [1]. Detection of esophageal cancer is the most effective strategy to improve its outcome [2]. Conventional white light endoscopy remains the gold standard surveillance procedure for premalignant conditions of the upper gastrointestinal tract, its cost-effectiveness is debated [3, 4]. The surveillance endoscopy, as mandated by the American College of Gastroenterology guidelines, yields ∼20 biopsies, most of which are normal on histologic assess-. Authors' Affiliations: Departments of 1Surgery and Cancer and 2Histopathology, Imperial College London, London, United Kingdom. Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/). D. Yakoub and H.C. Keun contributed to this work
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