Lurje Georg, Vallbohmer Daniel, Collet Peter H, Xi Huan, Baldus Stephan E, Brabender Jan, Metzger Ralf, Heitmann Michaela, Neiss Susanne, Drebber Ute, Holscher Arnulf H, Schneider Paul M
Department of Visceral and Vascular Surgery, University of Cologne, Cologne, Germany.
J Gastrointest Surg. 2007 Sep;11(9):1105-11. doi: 10.1007/s11605-007-0210-3. Epub 2007 Jul 10.
Little is known about the role of cyclooxygenase (COX)-2 in gastroesophageal reflux disease (GERD) and the development of Barrett's metaplasia. The objectives of this study were to further analyze COX-2 mRNA expression in patients with GERD compared to Barrett's esophagus (BE) and Barrett's cancer (BC).
Tissue samples from 110 patients with GERD (n = 43), BE (n = 20), and BC (n = 47) were obtained in routine upper GI endoscopy. Expression levels of COX-2 were measured by quantitative real-time reverse trancriptase polymerase chain reaction (RT-PCR). Also, 24-h pH monitoring was performed in all patients of the GERD study group and the DeMeester composite score was used to match COX-2 mRNA expression with the severity of acid exposure in the lower esophagus.
COX-2 mRNA is progressively upregulated within the metaplasia-dysplasia-adenocarcinoma (MDA) sequence (p = 0.001). COX-2 levels of the squamous epithelium in the distal esophagus from patients with GERD and a pathologic mean DeMeester score (>14.72) were significantly higher than in patients with normal DeMeester scores (p = 0.01).
In summary our findings suggest that alterations in COX-2 mRNA expression occur independently of endoscopic or histologic signs of GERD in the acid-exposed squamous epithelium of the distal esophagus. However, this early COX-2 increase in GERD is further upregulated within the MDA sequence for yet unknown reasons.
关于环氧化酶（COX）-2在胃食管反流病（GERD）及巴雷特化生发展中的作用，人们了解甚少。本研究的目的是进一步分析GERD患者与巴雷特食管（BE）和巴雷特癌（BC）患者相比COX-2 mRNA的表达情况。
在常规上消化道内镜检查中获取了110例GERD患者（n = 43）、BE患者（n = 20）和BC患者（n = 47）的组织样本。通过定量实时逆转录聚合酶链反应（RT-PCR）测量COX-2的表达水平。此外，对GERD研究组的所有患者进行了24小时pH监测，并使用DeMeester综合评分将COX-2 mRNA表达与食管下段酸暴露的严重程度进行匹配。
COX-2 mRNA在化生-发育异常-腺癌（MDA）序列中逐渐上调（p = 0.001）。GERD患者且病理平均DeMeester评分（>14.72）的食管远端鳞状上皮的COX-2水平显著高于DeMeester评分正常的患者（p = 0.01）。
总之，我们的研究结果表明，在食管远端酸暴露的鳞状上皮中，COX-2 mRNA表达的改变独立于GERD的内镜或组织学征象而发生。然而，GERD中这种早期的COX-2增加在MDA序列中因未知原因进一步上调。
