cular and Cellular Pathobiology abolic Profiling Detects Field Effects in Nondysplastic R ue from Esophageal Cancer Patients

Downlo variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectivef surveillance programs in esophageal cancer. Based on the “field cancerization” hypothesis that tumors ithin a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling differentiate between histologically normal tissue from individuals with and without esophageal cancer. -five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. H magic angle spinning–nuclear magnetic resonance spectroscopy of intact tissue, we generated olic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), oximal histologically normal mucosa from a control group. Using multivariate regression and receiveror characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically l tissues from cancer patients and from that of controls. Whereas 26% and 12% of the spectral profile s were uniquely discriminating tumor or control tissue, respectively, 5% of the profile exhibited a signifrogressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned sphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing unds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence phageal cancer (n = 123; area under the curve, 0.84; P < 0.001). In conclusion, our findings support the esis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. hypoth 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. Cancer Res; 70(22); 9129–36. ©2010 AACR.