In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer
In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer
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DOI：
10.1016/j.yexmp.2017.02.013
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发表时间：
2017-04-01
影响因子：
3.6
通讯作者：
Klapper, Wolfram
中科院分区：
文献类型：
--
作者：
Alkatout, Ibrahim;Huebner, Friederike;Klapper, Wolfram
目的：肿瘤手术的目的是彻底切除病灶，同时保证足够的肿瘤特异性安全距离。然而，在许多情况下，最外围的部分——入侵前沿——仍然留在原地。据报道，肿瘤边缘的肿瘤细胞失去了上皮特性并获得了间充质细胞的特征。上皮-间质转化（EMT）过程被认为对于组织和血管侵袭至关重要。此外，乳腺癌微环境中肿瘤浸润淋巴细胞的检测可能作为可靠的预后标志物。方法：我们研究了 352 名乳腺癌患者的组织微阵列，了解 EMT 因子 Snail 的存在和分布，以及免疫微环境中 FoxP3、CD3 和 CD8 的存在。结果：转录因子 Snail 的表达与较长的无病生存期和总生存期密切相关。 CD3、CD8 或 FoxP3 的存在与更好的结果相关，尽管只有 FoxP3 才发现具有统计学意义的结果。 FoxP3和Snail的预后意义也在多变量分析中得到证实。结论：基于之前关于EMT瘤内异质性的研究，我们的结果表明Snail和FoxP3可能是乳腺癌的预后标志物。证实了肿瘤微环境中存在多种淋巴细胞（CD3 和 CD8）。尽管这些标记物的重要性是已知的，但它们在肿瘤侵袭和转移中的具体作用以及它们在这些肿瘤中的分层组织仍不清楚。 (C) 2017 Elsevier Inc. 保留所有权利。
Purpose: Tumor surgery is aimed at complete resection of the lesion while ensuring a sufficient tumor-specific safety distance. Nevertheless, in many cases the most peripheral part - the invasion front - remains in situ. Tumor cells at the tumor margin have been reported to lose their epithelial properties and acquire features of mesenchymal cells. The process of epithelial-to-mesenchymal transition (EMT) is believed to be of prime importance for tissue and vessel invasion. Furthermore, the detection of tumor-infiltrating lymphocytes in the microenvironment of breast cancer might serve as a reliable prognostic marker.Methods: We investigated tissue microarrays of 352 breast cancer patients with regard to the presence and distribution of the EMT factor Snail, and the presence of FoxP3, CD3 and CD8 in the immune microenvironment.Results: The expression of the transcription factor Snail is strongly associated with longer disease-free and overall survival. The presence of CD3, CD8 or FoxP3 is associated with a better outcome, although statistically significant results were noted only for FoxP3. The prognostic significance of FoxP3 and Snail were also proven in multivariate analysis.Conclusions: Based on previous studies concerning the intratumoral heterogeneity of EMT, our results suggest that Snail and FoxP3 are possible prognostic markers for breast cancer. The diverse presence of lymphocytes in the tumor microenvironment (CD3 and CD8) was confirmed. Although the importance of these markers is known, their specific role in tumor invasion and metastasis as well as their hierarchical organization in these tumors remain unclear. (C) 2017 Elsevier Inc. All rights reserved.