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: E S Dellon, J J Bower, T O Keku, X Chen, C R Miller, J T Woosley, R C Orlando, N J Shaheen
• Journal: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus (Dis Esophagus) Vol. 25 Issue 2 Pg. 166-74 (Feb 2012) ISSN: 1442-2050 [Electronic] United States
• PMID: 21819482 (Publication Type: Journal Article)
• Copyright: © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Chemical References

• Biomarkers
• STAT5 Transcription Factor
• Receptor, Platelet-Derived Growth Factor alpha
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1

Topics

• Adolescent
• Adult
• Biomarkers (metabolism)
• Child
• Child, Preschool
• Cross-Sectional Studies
• Eosinophilic Esophagitis (genetics, metabolism)
• Female
• Gastroesophageal Reflux (genetics, metabolism)
• Humans
• In Situ Hybridization, Fluorescence
• Infant
• MAP Kinase Signaling System (physiology)
• Male
• Middle Aged
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Pilot Projects
• Receptor, Platelet-Derived Growth Factor alpha (genetics, metabolism)
• Retrospective Studies
• STAT5 Transcription Factor (genetics, metabolism)
• Young Adult