title: Markers of tyrosine kinase activity in eosinophilic esophagitis: a pilot study of the FIP1L1-PDGFRα fusion gene, pERK 1/2, and pSTAT5.
abstract: The pathogenesis of eosinophilic esophagitis (EoE) is incompletely understood. In certain eosinophilic diseases, activation of tyrosine kinase after fusion of the Fip1-like-1 and platelet-derived growth factor receptor-α genes (F-P fusion gene) mediates eosinophilia via downstream effectors such as extracellular-regulated kinase (ERK1/2) and signal transducers and activators of transcription (STAT5). This mechanism has not been examined in EoE. Our aim was to detect the F-P fusion gene, pERK1/2, and pSTAT5 in esophageal tissue from patients with EoE, gastroesophageal reflux disease (GERD), and normal controls. We performed a cross-sectional pilot study comparing patients with steroid-responsive and steroid-refractory EoE, to GERD patients and normal controls. EoE cases were defined by consensus guidelines. Fluorescence in situ hybridization (FISH) was performed to detect the F-P fusion gene and immunohistochemistry (IHC) was performed to detect pERK1/2 and pSTAT5 in esophageal biopsies. Twenty-nine subjects (median age 30 years [range 1-59]; 16 males; 24 Caucasians) were included: eight normal, six GERD, and 15 EoE (five steroid-refractory). On FISH, 98%, 99%, and 99% of the nuclei in the normal, GERD, and EoE groups, respectively, were normal (P= 0.42). On IHC, a median of 250, 277, and 479 nuclei/mm(2) stained for pERK 1/2 in the normal, GERD, and EoE groups, respectively (P= 0.07); the refractory EoE patients had the highest degree pERK 1/2 staining (846 nuclei/mm(2); P= 0.07). No trend was seen for pSTAT5. In conclusion, the F-P fusion gene was not detected with increased frequency in EoE. Patients with EoE had a trend toward higher levels of pERK 1/2, but not STAT5, in the esophageal epithelium, with highest levels in steroid-refractory EoE patients.
authors.affiliation: Center for Esophageal Diseases and Swallowing, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. edellon@med.unc.edu
authors.forename: E S
authors.initials: ES
authors.lastname: Dellon
authors.forename: J J
authors.initials: JJ
authors.lastname: Bower
authors.forename: T O
authors.initials: TO
authors.lastname: Keku
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: C R
authors.initials: CR
authors.lastname: Miller
authors.forename: J T
authors.initials: JT
authors.lastname: Woosley
authors.forename: R C
authors.initials: RC
authors.lastname: Orlando
authors.forename: N J
authors.initials: NJ
authors.lastname: Shaheen
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D057765:Eosinophilic Esophagitis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005764:Gastroesophageal Reflux / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D010865:Pilot Projects; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D050799:STAT5 Transcription Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1