Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa
Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa
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DOI：
10.1136/gut.50.3.373
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发表时间：
2002-03-01
期刊：
影响因子：
24.5
通讯作者：
Williams, GH
中科院分区：
文献类型：
--
作者：
Going, JJ;Keith, WN;Williams, GH
背景资料：微小染色体维持（Mcm）蛋白是真核生物DNA复制所必需的，它们的表达意味着细胞增殖的潜力。表达失调的异常状态，但食管鳞状粘膜和巴雷特的mucosa.Aim的数据尚未公布：为了测试的假设，即Mcm蛋白下调与增殖标记Ki-67在区分上皮细胞室的非异常鳞状和巴雷特的上皮，这一过程并不发生在异型增生的粘膜。方法和病例：45例Barrett食管患者包括20例腺体发育不良（10例低度，8例高度，2例两者兼有，4例浸润性腺癌）。其他25例患者包括12例食管鳞状上皮不典型增生（3例低度，6例高度，3例两者兼有，4例浸润性鳞状细胞癌）。使用Mcm 2、Mcm 5和Ki-67抗体对来自活检系列和切除的福尔马林固定石蜡包埋组织切片进行免疫染色。估计Mcm 2、Mcm 5和Ki-67阳性细胞核的百分比，并从0至6评分为：0，无+; 1，< 10%+; 2，10-30%+; 3，30-70%+; 4，70-90%+; 5，>90%+; 6，全部+。四个独立的上皮层进行了评分：在鳞状上皮的基底层和三分之一的表面，在Barrett的粘膜的腔面，上，下隐窝，和深glands.Results：在非发育不良的鳞状上皮和Barrett的粘膜，高水平表达的Mcm 2，Mcm 5，Ki-67蛋白主要局限于增殖车厢和下调分化车厢。表达持续到粘膜表面在异型增生鳞状上皮和Barrett's mucosal.Conclusions：持续表达的Mcm 2，Mcm 5，Ki-67蛋白在管腔室的异型增生食管鳞状上皮和异型增生Barrett's mucosal. Conclusions可能是诊断标志物，并意味着中断细胞周期控制和分化，这些异型增生上皮。
Background: Minichromosome maintenance (Mcm) proteins are essential for eukaryotic DNA replication, and their expression implies potential for cell proliferation. Expression is dysregulated in dysplastic states but data for oesophageal squamous mucosa and Barrett's mucosa have not been published.Aim: To test the hypothesis that Mcm proteins are downregulated together with the proliferation marker Ki-67 in differentiating epithelial compartments of non-dysplastic squamous and Barrett's epithelium, and that this process does not occur in dysplastic mucosae.Methods and cases: Forty five patients with Barrett's oesophagus included 20 with glandular dysplasia (10 low grade, eight high grade, two both, and four with invasive adenocarcinoma). Twenty five other patients included 12 with oesophageal squamous dysplasia (three low grade, six high grade, three both, and four with invasive squamous carcinoma). Formalin fixed paraffin embedded tissue sections from biopsy series and resections were immunostained using antibodies to Mcm2, Mcm5, and Ki-67. Percentage of nuclei positive for Mcm2, Mcm5, and Ki-67 was estimated and scored from 0 to 6 as: 0, none +; 1, < 10%+; 2, 10-30%+; 3, 30-70%+; 4, 70-90%+; 5, >90%+; 6, all+. Four separate epithelial strata were scored: in squamous epithelium the basal layer and thirds to the surface, in Barrett's mucosa the luminal surface, upper and lower crypt, and deep glands.Results: In non-dysplastic squamous epithelium and Barrett's mucosa, high level expression of Mcm2, Mcm5, and Ki-67 proteins was largely confined to the proliferative compartments and downregulated in differentiated compartments. Expression persisted up to the mucosal surface in dysplastic squamous epithelium and Barrett's mucosa.Conclusions: Persistent expression of Mcm2, Mcm5, and Ki-67 proteins in luminal compartments of dysplastic oesophageal squamous epithelium and dysplastic Barrett's mucosa may be diagnostic markers and imply disruption of cell cycle control and differentiation in these dysplastic epithelia.