Takai Masaaki, Terai Yoshito, Kawaguchi Hiroshi, Ashihara Keisuke, Fujiwara Satoe, Tanaka Tomohito, Tsunetoh Satoshi, Tanaka Yoshimichi, Sasaki Hiroshi, Kanemura Masanori, Tanabe Akiko, Ohmichi Masahide
J Ovarian Res. 2014 Jul 27;7:76. doi: 10.1186/1757-2215-7-76.
The epithelial-mesenchymal-transition (EMT) is an important step in the invasion and metastasis of cancer. A critical molecular feature of this process is the downregulation of the E-cadherin expression, which is primarily controlled by Snail-related zinc-finger transcription factors. The aim of this study was to evaluate the prognostic impact of the expression of EMT-related proteins (E-cadherin and Snail) in patients with ovarian cancer.
An immunohistochemical analysis was conducted using tissue microarray samples of 174 primary tumors and 34 metastases of ovarian carcinoma, and the relationships between the protein expression, clinicopathological features and outcomes were investigated.
A reduced E-cadherin expression was observed in 36.8% of the primary tumors and 30.4%, 35.7%, 37.7% and 52.7% of the stage I, II, III and IV tumors, respectively. The nuclear expression of Snail was positive in 33.9% of the primary tumors. The rate of an EMT-positive status, as represented by both a reduced E-cadherin expression and a nuclear expression of Snail, was significantly higher in the patients with peritoneal dissemination than in those without (p < 0.05). The EMT status was significantly associated with both the progression-free survival and overall survival (p <0.01). A multivariate analysis showed an EMT-positive status to be a significant predictor of both the progression-free survival (p < 0.05) and overall survival (P < 0.01).
These data indicate that the EMT status is significantly associated with peritoneal metastasis and both the progression-free survival and overall survival in patients with ovarian cancer. Therefore, clarifying and controlling EMT signaling is a promising approach to molecular targeted therapy for ovarian cancer.
上皮-间质转化（EMT）是癌症侵袭和转移的重要步骤。该过程的一个关键分子特征是E-钙黏蛋白表达下调，这主要由Snail相关锌指转录因子控制。本研究旨在评估EMT相关蛋白（E-钙黏蛋白和Snail）表达对卵巢癌患者的预后影响。
使用174例原发性肿瘤和34例卵巢癌转移灶的组织微阵列样本进行免疫组化分析，研究蛋白表达、临床病理特征与预后之间的关系。
在36.8%的原发性肿瘤中观察到E-钙黏蛋白表达降低，在Ⅰ、Ⅱ、Ⅲ和Ⅳ期肿瘤中分别为30.4%、35.7%、37.7%和52.7%。33.9%的原发性肿瘤中Snail核表达呈阳性。以E-钙黏蛋白表达降低和Snail核表达表示的EMT阳性状态在腹膜播散患者中的发生率显著高于无腹膜播散患者（p<0.05）。EMT状态与无进展生存期和总生存期均显著相关（p<0.01）。多因素分析显示，EMT阳性状态是无进展生存期（p<0.05）和总生存期（p<0.01）的显著预测指标。
这些数据表明，EMT状态与卵巢癌患者的腹膜转移、无进展生存期和总生存期均显著相关。因此，阐明和控制EMT信号通路是卵巢癌分子靶向治疗的一种有前景的方法。
