Section of Gastrointestinal Surgery, Parc de Salut Mar and Institut de Recerca Hospital del Mar (IMIM-Hospital del Mar), Universitat Autònoma de Barcelona, Passeig Maritim 25-29, 08003, Barcelona, Spain.
J Gastrointest Surg. 2012 Feb;16(2):227-37; discussion 237. doi: 10.1007/s11605-011-1758-5. Epub 2011 Nov 11.
A human model of gastroesophageal reflux disease was used to examine the contribution of a non-specialized columnar type of metaplasia (NSCM) and key molecular events (BMP4 and CDX2) in the development of Barrett's esophagus.
Biopsies of the remnant esophagus from 18 patients undergoing esophagectomy with gastric preservation were taken at 6-36-month intervals postoperatively and examined for activation of the BMP pathway (BMP4/P-Smad 1/5/8) and CDX2 and CDX1 expression by imunohistochemistry, quantitative real-time PCR, Western blot, and in situ hybridization.
A short segment (mean 15.6 mm) of NSCM was detected in 10 (56%) patients, with an increasing prevalence from 17% at 6 months to 62% at 36 months. Nuclear expression of P-Smad 1/5/8 in the squamous epithelium close to the anastomosis with strong expression in all epithelial cells of NSCM areas was found. Forty-eight (63%) biopsies with NSCM showed scattered nuclear expression of CDX2. Two cases showed isolated glands at 18, 24, and 36 months that fully expressed CDX2 and co-expressed CDX1. BMP4 mRNA and CDX2 mRNA levels were significantly greater in NSCM than in squamous epithelium.
BMP4 activation in NSCM and early expression of CDX2 are involved in the columnar epithelial differentiation of Barrett's esophagus.
本研究采用胃食管反流病的人类模型，旨在探讨非特异性柱状化生（NSCM）和关键分子事件（BMP4 和 CDX2）在 Barrett 食管发生过程中的作用。
收集 18 例行保留胃的食管切除术患者的残食管活检标本，在术后 6-36 个月的时间间隔内进行检测，通过免疫组化、实时定量 PCR、Western blot 和原位杂交检测 BMP 通路（BMP4/P-Smad 1/5/8）和 CDX2、CDX1 的表达情况。
在 10 例（56%）患者中检测到短节段（平均 15.6mm）NSCM，其发生率从术后 6 个月的 17%逐渐增加到 36 个月的 62%。在吻合口附近的鳞状上皮中发现 P-Smad 1/5/8 的核表达，而在 NSCM 区域的所有上皮细胞中均有强烈表达。在 48 例（63%）有 NSCM 的活检标本中，CDX2 呈散在核表达。2 例在术后 18、24 和 36 个月时出现孤立的腺管，完全表达 CDX2 并共表达 CDX1。NSCM 中的 BMP4 mRNA 和 CDX2 mRNA 水平明显高于鳞状上皮。
NSCM 中的 BMP4 激活和 CDX2 的早期表达参与了 Barrett 食管柱状上皮的分化。
