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上皮细胞黏附分子、CD44、CD133 和 CD166 的表达对 Vater 壶腹肿瘤患者生存的影响。

Effect of EpCAM, CD44, CD133 and CD166 expression on patient survival in tumours of the ampulla of Vater.

机构信息

Institute of Pathology, University Hospital of Basel, Basel, Switzerland.

出版信息

J Clin Pathol. 2012 Feb;65(2):140-5. doi: 10.1136/jclinpath-2011-200043. Epub 2011 Nov 30.

Abstract

BACKGROUND

Carcinomas of the Vaterian system are rare and presumably arise from pre-existing adenomas. According to the cancer stem cell (CSC) hypothesis, only a small subset of tumor cells has the ability to initiate and develop tumor growth. In colorectal cancer, CD44, CD133, CD166 and EpCAM have been proposed to represent CSC marker proteins and their expression has been shown to correlate with patient survival.

AIMS

To evaluate a potential role of these CSC proteins in tumors of the ampulla of Vater, we investigated their expression in 175 carcinoma, 111 adenoma and 152 normal mucosa specimens arranged in a Tissue Microarray format.

MATERIALS AND METHODS

Membranous immunoreactivity for each protein marker was scored semi-quantitatively by evaluating the number of positive tumor cells over the total number of tumor cells. Median protein expression levels were used as cut-off scores to define protein marker positivity. Clinical data including survival time were obtained by retrospective analysis of medical records, tumor registries or direct contact.

RESULTS

The expression of all evaluated marker proteins differed significantly between normal mucosa, adenoma and carcinoma samples. In all markers, we found a tendency towards more constant expression from normal to neoplastic tissue. EpCAM expression was significantly correlated with better patient survival. The increased expression of CD44s, CD166 and CD133 from normal mucosa samples to adenoma and carcinoma was linked to tumor progression. However, there was no statistically significant correlation with survival.

CONCLUSION

Our findings indicate, that in ampullary carcinomas, loss of expression of EpCAM may be linked to a more aggressive tumor phenotype.

摘要

背景

Vater 系统的癌很少见,推测起源于先前存在的腺瘤。根据癌症干细胞(CSC)假说,只有一小部分肿瘤细胞具有启动和发展肿瘤生长的能力。在结直肠癌中,CD44、CD133、CD166 和 EpCAM 被认为是 CSC 标记蛋白,其表达与患者的生存相关。

目的

为了评估这些 CSC 蛋白在 Vater 壶腹肿瘤中的潜在作用,我们在组织微阵列中评估了 175 例癌、111 例腺瘤和 152 例正常黏膜标本中这些 CSC 蛋白的表达。

材料和方法

通过评估阳性肿瘤细胞数与总肿瘤细胞数的比值,对每种蛋白标记物的膜免疫反应进行半定量评分。将蛋白标记物的阳性表达定义为使用中位数蛋白表达水平作为截断分数。通过回顾性分析病历、肿瘤登记或直接联系,获得包括生存时间在内的临床数据。

结果

所有评估的标记蛋白在正常黏膜、腺瘤和癌组织样本之间的表达差异显著。在所有标记物中,我们发现从正常组织到肿瘤组织的表达呈更稳定的趋势。EpCAM 的表达与患者的生存时间显著相关。CD44s、CD166 和 CD133 从正常黏膜样本到腺瘤和癌组织的表达增加与肿瘤进展相关。然而,与生存没有统计学上的显著相关性。

结论

我们的研究结果表明,在壶腹癌中,EpCAM 的表达缺失可能与更具侵袭性的肿瘤表型有关。

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