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Claudin 表达变化对伴有区域淋巴结转移的乳腺癌的预后意义。

Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis.

机构信息

2nd Department of Pathology, Semmelweis University, Ulloi ut 93, Budapest 1091, Hungary.

出版信息

Clin Exp Metastasis. 2011 Jan;28(1):55-63. doi: 10.1007/s10585-010-9357-5. Epub 2010 Oct 21.

DOI:10.1007/s10585-010-9357-5
PMID:20963473
Abstract

Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated semiquantitatively. When compared to LNMs, in the IDC group beta-catenin and claudin-2, -3, -4 and -7 protein expression showed different pattern while claudin-1, -2, -3, -4 and -7 were differently expressed in the ILC group. Lymph node metastases developed a notable increase of claudin-5 expression in both groups. Decrease or loss of claudin-1 and expression of claudin-4 in lymph node metastases correlated with reduced disease-free survival in our patients. According to our observations, the expression of epithelial junctional molecules, especially claudins, is different in primary breast carcinomas compared to their lymph node metastases as demonstrated by immunohistochemistry. Loss of claudin junctional molecules might contribute to tumor progression, and certain claudin expression pattern might be of prognostic relevance.

摘要

黏附连接和紧密连接分子已被描述为有助于癌症的发生和肿瘤的进展。此外,最近已经确定 Claudin-low 肿瘤群作为乳腺癌的一个分子亚群。在我们的研究中,我们检查了 Claudin、β-连环蛋白和 E-钙黏蛋白在浸润性导管癌(IDCs)和小叶癌(ILCs)及其相应的淋巴结转移(LNMs)中的表达模式。使用组织微阵列对 97 例乳腺样本(60 例浸润性导管癌、37 例浸润性小叶癌)及其相应的 LNMs 进行了免疫组织化学分析,以检测 Claudin-1、-2、-3、-4、-5、-7、β-连环蛋白和 E-钙黏蛋白的表达。用幻灯片扫描仪对染色的幻灯片进行数字化,并对反应进行半定量评估。与 LNMs 相比,在 IDC 组中,β-连环蛋白和 Claudin-2、-3、-4 和 -7 蛋白表达显示出不同的模式,而 Claudin-1、-2、-3、-4 和 -7 在 ILC 组中表达不同。淋巴结转移在两组中均表现出 Claudin-5 表达的显著增加。在我们的患者中,淋巴结转移中 Claudin-1 和 Claudin-4 的表达减少或缺失与无病生存率降低相关。根据我们的观察,与淋巴结转移相比,原发性乳腺癌中上皮连接分子的表达,特别是 Claudin 的表达通过免疫组织化学显示出不同。Claudin 连接分子的缺失可能有助于肿瘤的进展,某些 Claudin 表达模式可能具有预后相关性。

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