A Gene Expression Profile Test (EoGenius) for the Diagnosis of Eosinophilic Esophagitis Shows Excellent Correlation with Histological Findings of Esophageal Biopsies

Abstract

Introduction: Eosinophilic esophagitis (EoE) can be difficult to differentiate clinically from other causes of dysphagia and heartburn. A new gene expression profile test (EoGenius) has been shown to distinguish EoE from other conditions in controlled prospective clinical studies conducted in children and some adults. The aim of this study was to evaluate the performance of EoGenius in the clinical setting of a pediatric gastroenterology practice. Methods: EoGenius was performed using formalin-fixed paraffin embedded samples of esophageal biopsy collected during a diagnostic EGD. RNA was extracted, gene expression for a 94 gene panel was quantified, and a summary expression score was calculated by adding the differences between housekeeping genes and each gene value. The area under the receiver operating curve was calculated and results were expressed as positive or negative. In one arm of the study results of EoGenius were compared to the clinicopathologic diagnosis in a series of children with no previous diagnosis of EoE. Patients were considered as having EoE if they met the clinical and histopathologic criteria established by the 2013 AGA consensus. In a second arm, results of EoGenius were compared to those of biopsies in a group of children previously diagnosed with EoE and given treatment. For both study arms, positive (PPV) and negative predictive values (NPV) were calculated. Results: The first arm included 10 children. EoGenius was positive in 5, all with clinical and histopathologic EoE, and negative in 5 other children, all with non-diagnostic biopsies (eos/HPF < 15 in all cases). Thus, in untreated EoE, EoGenius had a 100% PPV and 100% NPV. The second arm included 26 children. EoGenius was positive in 16: 14 had biopsies diagnostic of EoE (presumed non-responders) and 2 had negative biopsies (presumed responders). Thus, EoGenius identified correctly 88% of the nonresponders. In contrast, EoGenius was negative in 10 children, 6 responders and 4 non-responders, with a NPV of 60%. Conclusion: In treatment-naive EoE patients, EoGenius showed perfect correspondence with the biopsy results. In contrast, 4 of 10 treated patients who had not decreased their eos/HPF numbers during treatment were still positive, whereas 2 of 26 who had no longer histological EoE (< 15 eos/HPF) still had a positive test. Clinical follow up studies are currently being carried out to determine whether EoGenius or the numbers of eosinophils is more accurate in predicting long-term response.