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应用染色内镜检测 CK7、CK20、p53、Ki67 和 COX2 的表达评估 Barrett 食管。

Evaluation of Barrett's esophagus with CK7, CK20, p53, Ki67, and COX2 expressions using chromoendoscopical examination.

机构信息

Department of Gastroenterology, Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey.

出版信息

Dis Esophagus. 2013 Feb-Mar;26(2):189-96. doi: 10.1111/j.1442-2050.2012.01352.x. Epub 2012 May 16.

Abstract

Barrett's esophagus (BE) is a complication of chronic gastroesophageal reflux disease and can be diagnosed when there is an endoscopically irregular Z-line and intestinal metaplasia (IM) in a biopsy obtained lower esophagus. It is still not clear whether IM in the gastric cardia or columnar mucosa without IM in the lower esophagus have any significance as BE, which is considered as preneoplastic. The aim of the study was to determine the immunohistochemical features of BE and columnar mucosa in the distal esophagus and also to evaluate the value of chromoendoscopy in the diagnosis of BE in a prospective manner. A total of 12 chromoendoscopic biopsies (six from normal-looking unstained esophagus and six from esophageal mucosa stained with methyl blue suspicious of BE) were taken from 111 cases who underwent endoscopy because of a variety of upper gastrointestinal symptoms. Immunohistochemical analysis was performed using CK7, CK20, p53, Ki67, and cyclooxygenase 2 (COX2). Of the 111 cases, 19 cases with carcinoma (nine adeno, six squamous, four undifferentiated carcinomas) and 17 cases with normal squamous epithelium were excluded, while 75 cases showing columnar epithelium, including 46 (61.3%) with IM and 29 (38,7%) without IM, were further evaluated immunohistochemically. CK7 was observed in surface, crypt, and glandular epithelium, whereas CK20 was expressed in surface and superficial crypt epithelium. No significant difference was observed between the Barrett and non-Barrett type of CK7/20 staining pattern (P > 0,05). Expression of p53 did not show any difference between BE and columnar mucosa without IM, whereas COX2 expression was significantly increased in BE (P < 0.05) in comparison with columnar mucosa without IM. Ki67 expression was significiantly higher both in upper and lower crypts in BE (P < 0.05). The present study showed that a Barrett pattern does not seem to exist; however, the analysis of COX2 expression and the Ki67 proliferation fraction by immunohistochemistry can be used to separate BE from non-Barrett's metaplasia of the distal esophagus. In our point of view, the immunohistochemical detection of p53 expression in Barrett's metaplasia stage is useless as a marker for early detection of high-risk patients.

摘要

巴雷特食管(BE)是慢性胃食管反流病的并发症,当食管下段内镜下可见不规则 Z 线和肠上皮化生(IM)时即可诊断。目前尚不清楚胃贲门处的 IM 或下段食管无 IM 的柱状黏膜是否与被认为是癌前病变的 BE 具有相同意义。本研究旨在确定 BE 及食管下段柱状黏膜的免疫组织化学特征,并前瞻性评估染色内镜在 BE 诊断中的价值。对因各种上消化道症状而行内镜检查的 111 例患者,共进行了 12 次染色内镜活检(6 次取自外观正常未染色食管,6 次取自疑似 BE 而用甲蓝染色的食管黏膜)。采用 CK7、CK20、p53、Ki67 和环氧化酶 2(COX2)进行免疫组织化学分析。111 例患者中,19 例(9 例腺癌、6 例鳞癌、4 例未分化癌)合并癌及 17 例正常鳞上皮被排除,而进一步进行免疫组化评估的 75 例患者表现为柱状上皮,其中 46 例(61.3%)伴 IM,29 例(38.7%)无 IM。CK7 可见于表面、隐窝和腺上皮,而 CK20 表达于表面和浅层隐窝上皮。CK7/20 染色模式在 BE 和无 IM 的柱状黏膜之间无显著差异(P>0.05)。p53 在 BE 和无 IM 的柱状黏膜之间无差异,而 COX2 表达在 BE 中显著增加(P<0.05),与无 IM 的柱状黏膜相比。Ki67 在 BE 的上、下隐窝中表达均显著升高(P<0.05)。本研究表明,似乎不存在 Barrett 模式;然而,通过免疫组织化学分析 COX2 表达和 Ki67 增殖分数可将 BE 与食管下段无 Barrett 化生区分开。在我们看来,p53 表达的免疫组织化学检测在 Barrett 化生阶段作为高危患者早期检测的标志物是无用的。

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