Cao Yu-Wen, Wan Guo-Xing, Sun Jian-Ping, Cui Xiao-Bin, Hu Jian-Ming, Liang Wei-Hua, Zheng Yu-Qin, Li Wen-Qin, Li Feng
Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Kaohsiung J Med Sci. 2015 Feb;31(2):70-6. doi: 10.1016/j.kjms.2014.11.008. Epub 2014 Dec 16.
Emerging evidence suggests that activation of the Notch1 signaling pathway inducing epithelial to mesenchymal transition (EMT) mediated by Snail/Slug promotes invasion and metastasis of breast cancer cells in vitro. However, the implication of the Notch1-Snail/Slug-EMT axis in breast cancer patients remains unclear. A total of 200 formalin-fixed paraffin-embedded samples of invasive ductal carcinoma (IDC), and 37 adjacent non-neoplastic tissue (ANNT) samples from patients who had not been treated with neoadjuvant therapy were examined. Expression of Notch1, Slug, Snail, E-cadherin, N-cadherin, and vimentin was determined by immunohistochemistry on tissue microarrays (TMAs). The correlation between protein expression and clinicopathological characteristics of breast cancer patients was also evaluated. Results showed that a significantly high percentage of cases with high expression of Notch1 (74%, 148/200), Slug (36%, 72/200), Snail (62%, 124/200), and N-cadherin (77%, 153/200) and a low percentage of cases with high expression of E-cadherin (27%, 54/200) were observed in IDC compared to those in ANNTs. High Notch1, Slug, Snail, and N-cadherin expression and low E-cadherin expression in patients with IDC were significantly correlated with lymph node metastasis. In addition, correlation analysis results revealed that high Notch1 expression was significantly associated with high Slug, Snail, and N-cadherin expression and low E-cadherin expression in IDC. Furthermore, a high Snail expression was significantly associated with low E-cadherin expression, and a high Slug expression was found to be significantly associated with increased N-cadherin expression in patients with IDC. Hence, our study suggested that the Notch1-Snail/Slug-EMT axis may be implicated in the lymph node metastasis affecting patients with IDC.
新出现的证据表明，Notch1信号通路的激活通过Snail/Slug诱导上皮-间质转化（EMT），促进乳腺癌细胞在体外的侵袭和转移。然而，Notch1-Snail/Slug-EMT轴在乳腺癌患者中的意义仍不清楚。本研究共检测了200例浸润性导管癌（IDC）的福尔马林固定石蜡包埋样本，以及37例未接受新辅助治疗患者的癌旁非肿瘤组织（ANNT）样本。通过组织芯片（TMA）上的免疫组织化学法检测Notch1、Slug、Snail、E-钙黏蛋白、N-钙黏蛋白和波形蛋白的表达。还评估了蛋白表达与乳腺癌患者临床病理特征之间的相关性。结果显示，与ANNT相比，IDC中Notch1（74%，148/200）、Slug（36%，72/200）、Snail（62%，124/200）和N-钙黏蛋白（77%，153/200）高表达的病例比例显著较高，而E-钙黏蛋白高表达的病例比例较低（27%，54/200）。IDC患者中Notch1、Slug、Snail和N-钙黏蛋白高表达以及E-钙黏蛋白低表达与淋巴结转移显著相关。此外，相关性分析结果显示，IDC中Notch1高表达与Slug、Snail和N-钙黏蛋白高表达以及E-钙黏蛋白低表达显著相关。此外，Snail高表达与E-钙黏蛋白低表达显著相关，而Slug高表达与IDC患者N-钙黏蛋白表达增加显著相关。因此，我们的研究表明，Notch1-Snail/Slug-EMT轴可能与影响IDC患者的淋巴结转移有关。
