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上皮-间充质转化标志物在胃肠胰神经内分泌肿瘤鉴别诊断中的应用。

Epithelial-mesenchymal transition markers in the differential diagnosis of gastroenteropancreatic neuroendocrine tumors.

机构信息

Laboratorio del Banco de Tumores-Anatomia Patológica, c/ Celestino Villamil, s/n, 33006 Oviedo, Spain.

出版信息

Am J Clin Pathol. 2013 Jul;140(1):61-72. doi: 10.1309/AJCPIV40ISTBXRAX.

DOI:10.1309/AJCPIV40ISTBXRAX
PMID:23765535
Abstract

OBJECTIVES

To elucidate the role of epithelial-mesenchymal transition markers in gastroenteropancreatic neuroendocrine tumors (GEP NETs) and the potential usefulness in their clinical management.

METHODS

One hundred ten GEP NET paraffin-embedded samples were immunohistochemically analyzed for E-cadherin, N-cadherin, β-catenin, vimentin, Snail1, Snail2, Twist, and Foxc2 protein expression.

RESULTS

The 5-year survival rate was reduced for those patients showing high Snail1 protein levels, a cytoplasmic E-cadherin pattern, reduced N-cadherin expression, and loss of E-cadherin/β-catenin adhesion complex integrity at the cell membrane. Interestingly, high β-catenin expression was useful in identifying a grade 1 NET subgroup with a favorable clinical course. Importantly, it also helped to discriminate small-cell vs large-cell grade 3 neuroendocrine carcinomas.

CONCLUSIONS

β-Catenin and N-cadherin immunohistochemical detection might be a useful tool in the differential diagnosis of small-cell vs large-cell G3 neuroendocrine carcinomas. High Snail1 and Foxc2 expression is associated with the invasion and metastatic spread of GEP NETs.

摘要

目的

阐明上皮-间充质转化标志物在胃肠胰神经内分泌肿瘤(GEP NET)中的作用及其在临床管理中的潜在应用价值。

方法

对 110 例 GEP NET 石蜡包埋样本进行免疫组织化学分析,检测 E-钙黏蛋白、N-钙黏蛋白、β-连环蛋白、波形蛋白、Snail1、Snail2、Twist 和 Foxc2 蛋白的表达。

结果

那些 Snail1 蛋白水平高、细胞质 E-钙黏蛋白模式、N-钙黏蛋白表达降低以及细胞膜上 E-钙黏蛋白/β-连环蛋白黏附复合物完整性丧失的患者,5 年生存率降低。有趣的是,高β-连环蛋白表达有助于识别具有良好临床过程的 1 级 NET 亚组。重要的是,它还有助于区分小细胞与大细胞 3 级神经内分泌癌。

结论

β-连环蛋白和 N-钙黏蛋白免疫组织化学检测可能是鉴别小细胞与大细胞 G3 神经内分泌癌的有用工具。高 Snail1 和 Foxc2 表达与 GEP NET 的侵袭和转移扩散有关。

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