Correlation of the Eosinophilic Histopathological Scoring System with Esophageal Gene Expression in Patients with Eosinophilic Esophagitis
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Tetsuo Shoda, MD, PhD, Ting Wen, PhD, Julie M Caldwell, PhD, Jonathan Kuhl, Seema S. Aceves, MD PhD FAAAAI, Peter Bonis, MD, Kelley E. Capocelli, MD, Margaret H Collins, MD, Evan S. Dellon, MD MPH, Gary W Falk, MD, Glenn Furuta, MD, Nirmala Gonsalves, MD, Sandeep Gupta, MD FAAAAI, Ikuo Hirano, MD, John Leung, MD, Paul Menard-Katcher, Jonathan M. Spergel, MD PhD FAAAAI, Barry K. Wershil, Guang-Yu Yang, Marc E Rothenberg, MD PhD FAAAAI
RATIONALE: Eosinophilic esophagitis (EoE) is characterized by marked esophageal eosinophilia with a unique molecular signature. The EoE Histologic Scoring System (HSS), comprised of 8 histological domains scored on 4-point scale that express severity (grade) or extent (stage), provides a comprehensive measure of histopathological changes. However, correlation of the HSS domains to esophageal gene expression in EoE has not been previously studied.

METHODS: We evaluated 115 distal esophageal samples from children/adults with EoE enrolled in multi-center prospective study associated with Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Histological features were assessed by the peak eosinophil counts (PEC) and the HSS. Transcriptomic signature in esophageal biopsies were analyzed using a 96-gene EoE diagnostic panel (EDP).

RESULTS: Median HSS final grade and stage scores were 0.23 (range 0 – 0.86) and 0.23 (range 0 – 0.75), respectively. PEC significantly correlated with the 8 HSS domains for grade and stage (r = 0.3 – 0.9, P < 0.001). Of the 8 HSS domains, basal zone hyperplasia (BZH) showed the strongest correlation with the overall EDP expression (absolute median Spearman r = 0.54, 96 genes), as compared to other 7 domains. Moreover, we found that EoE patients have 4 endotypes as assessed by their molecular signatures, with each endotype associated with a unique HSS range.

CONCLUSIONS: BZH domain best reflects molecular signature changes in EoE compared with the 7 other HSS domains. This suggests that closer attention should be given to BZH when evaluating EoE activity.