Department of Medical Diagnostic Sciences & Special Therapies, Pathology Unit, University of Padova, Padova, Italy.
J Exp Clin Cancer Res. 2009 Aug 7;28(1):108. doi: 10.1186/1756-9966-28-108.
Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis.
The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: <10 weeks; Group B: 10-30 weeks; Group C: >30 weeks).
No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001).
De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.
巴雷特黏膜是食管腺癌的前身。巴雷特癌发生的分子机制在很大程度上尚不清楚。长期反流胃十二指肠内容物的实验性食管模型可能为巴雷特肿瘤发生的生物学序列提供重要信息。
在巴雷特癌发生的大鼠模型中评估 CDX2 hox 基因产物的表达。74 只大鼠行保留胃的食管空肠吻合术。排除围手术期死亡后，在手术后的不同时间点（A 组：<10 周；B 组：10-30 周；C 组：>30 周）对动物进行处死。
近端食管的鳞状上皮或鳞状细胞癌中均未检测到 Cdx2 表达。在反流性溃疡（A 组：68%；B 组：64%；C 组：80%）、多层上皮和肠上皮化生（A 组：9%；B 组：41%；C 组：60%）以及食管腺癌（B 组：36%；C 组：35%）中，在鳞状上皮的增生区始终有新的 Cdx2 表达。在实验过程中，总的 Cdx2 表达呈上升趋势（p=0.001）。
Cdx2 的新生表达是实验性胃食管反流诱导病变谱中的早期事件，应被视为食管腺癌形态发生的关键步骤。
