Center for Esophageal Diseases and Swallowing, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Dis Esophagus. 2012 Feb;25(2):166-74. doi: 10.1111/j.1442-2050.2011.01230.x. Epub 2011 Aug 5.
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.
嗜酸粒细胞性食管炎（EoE）的发病机制尚不完全清楚。在某些嗜酸性疾病中，Fip1 样-1 和血小板衍生生长因子受体-α 基因（F-P 融合基因）融合后酪氨酸激酶的激活通过细胞外调节激酶（ERK1/2）和信号转导子和转录激活子（STAT5）等下游效应物介导嗜酸性粒细胞增多。这一机制尚未在 EoE 中进行研究。我们的目的是检测 EoE、胃食管反流病（GERD）和正常对照组患者食管组织中的 F-P 融合基因、pERK1/2 和 pSTAT5。我们进行了一项横断面试点研究，比较了激素反应性和激素难治性 EoE 患者、GERD 患者和正常对照组。EoE 病例根据共识指南定义。荧光原位杂交（FISH）用于检测 F-P 融合基因，免疫组织化学（IHC）用于检测食管活检中的 pERK1/2 和 pSTAT5。29 名受试者（中位年龄 30 岁[范围 1-59]；16 名男性；24 名白种人）纳入研究：8 名正常对照、6 名 GERD 患者和 15 名 EoE 患者（5 名激素难治性）。在 FISH 中，正常组、GERD 组和 EoE 组分别有 98%、99%和 99%的核正常（P=0.42）。在 IHC 中，正常组、GERD 组和 EoE 组分别有 250、277 和 479 个核/mm²被 pERK1/2 染色（P=0.07）；激素难治性 EoE 患者的 pERK1/2 染色程度最高（846 个核/mm²；P=0.07）。pSTAT5 无趋势。总之，EoE 中未发现 F-P 融合基因的频率增加。EoE 患者食管上皮 pERK1/2 水平呈上升趋势，但 STAT5 无趋势，激素难治性 EoE 患者 pERK1/2 水平最高。
