Ahmad J, Arthur K, Maxwell P, Kennedy A, Johnston B T, Murray L, McManus D T
Belfast Health and Social Care Trust, Queens University Belfast, Royal Victoria Hospital, Belfast, UK.
Dis Esophagus. 2015 Apr;28(3):276-82. doi: 10.1111/dote.12181. Epub 2014 Feb 25.
The incidence of esophageal adenocarcinoma has increased dramatically over recent years and Barrett's esophagus is considered the most established risk factor for its development. Endoscopic surveillance of Barrett's esophagus is therefore recommended but hinges on histological interpretation of randomly taken biopsies which is poorly reproducible. The use of biomarkers presents an opportunity to improve our ability to risk-stratify these patients.We examined three biomarkers namely p504s, CD133, and Twist in the setting of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma to evaluate differential expression between benign, dysplastic, and malignant Barrett's tissue in an exploratory cross-sectional study. Twenty-five cases each of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma were included along-with 25 cases of esophagectomy resections for Barrett's adenocarcinoma. The biomarkers were immunostained on automated Ventana(®) immunostainer. The biopsies were assessed for biomarker expression by two independent observers. Granular cytoplasmic staining of p504s was observed in dysplastic Barrett's biopsies and esophageal adenocarcinoma but not in Barrett's esophagus. Apical and membranous CD133 expression was also observed in dysplastic Barrett's and esophageal adenocarcinoma. Nuclear Twist expression was seen predominantly in stromal cells. There was increased p504s expression in dysplastic Barrett's esophagus and esophageal adenocarcinoma compared with controls. CD133 expression was detected for the first time in esophageal adenocarcinoma and dysplastic Barrett's esophagus. Twist expression was not convincing enough to be labeled as Barrett's biomarker. p504s and CD133 have the potential to differentiate benign from malignant Barrett's tissue in this exploratory study. Their validity should be established in prospective longitudinal studies.
近年来，食管腺癌的发病率急剧上升，而巴雷特食管被认为是其发生发展最明确的危险因素。因此，建议对巴雷特食管进行内镜监测，但这取决于对随机活检组织的组织学解读，而这种解读的可重复性较差。生物标志物的应用为提高我们对这些患者进行风险分层的能力提供了契机。在一项探索性横断面研究中，我们检测了三种生物标志物，即p504s、CD133和Twist，用于巴雷特食管、低级别异型增生和食管腺癌的研究，以评估良性、异型增生和恶性巴雷特组织之间的差异表达。纳入了25例巴雷特食管、低级别异型增生和食管腺癌病例，以及25例因巴雷特腺癌行食管切除术的病例。这些生物标志物在自动Ventana(®)免疫染色仪上进行免疫染色。由两名独立观察者对活检组织的生物标志物表达进行评估。在异型增生的巴雷特活检组织和食管腺癌中观察到p504s的颗粒状细胞质染色，但在巴雷特食管中未观察到。在异型增生的巴雷特组织和食管腺癌中也观察到顶端和膜性CD133表达。核Twist表达主要见于基质细胞。与对照组相比，异型增生的巴雷特食管和食管腺癌中p504s表达增加。在食管腺癌和异型增生的巴雷特食管中首次检测到CD133表达。Twist表达不足以令人信服地被标记为巴雷特生物标志物。在这项探索性研究中，p504s和CD133有可能区分良性和恶性巴雷特组织。它们的有效性应在前瞻性纵向研究中得到证实。
