Endocrine Oncology Unit, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil.
Endocrinology Section, Federal Hospital of Lagoa, Rio de Janeiro, Brazil.
Endocrine. 2017 Nov;58(2):276-288. doi: 10.1007/s12020-017-1409-z. Epub 2017 Sep 8.
Epithelial-mesenchymal transition (EMT) is a biological dynamic process by which epithelial cells lose their epithelial phenotype and acquire mesenchymal invasive and migratory characteristics. This has been postulated as an essential step during cancer progression and metastasis. Although this is well described in other tumors, the role of EMT in adrenocortical tumors (ACT) has yet to be addressed.
The aim of this study was to evaluate the expression of EMT markers e-cadherin, vimentin, and fibronectin, along with EMT-transcription factors (EMT-TFs), TWIST1, SIP1, and SNAIL in 24 adrenocortical carcinoma (ACC), 19 adrenocortical adenomas (ACA), 27 childhood-onset adrenocortical tumors (CAT), and 12 normal adrenal glands. The association of EMT and EMT-TFs with clinical outcomes and pathology features were also evaluated.
Cytoplasmic vimentin expression was increased among CAT samples when compared to ACC, ACA, and normal adrenal samples (p < 0.001). There was no difference in e-cadherin and fibronectin expression observed between groups. Nuclear and cytoplasmic expression of TWIST1 and SIP1 was stronger in CAT and ACC vs. ACA and normal tissue samples (all, p < 0.05). ACT, regardless of classification, exhibited increased SNAIL expression when compared to normal tissue (p < 0.05). A significant correlation was observed between vimentin and TWIST1 (r = 0.44, p < 0.001); SIP1 (r = 0.51, p < 0.001); and SNAIL (r = 0.23, p < 0.05). TWIST1 and SIP1 expressions demonstrated a significant correlation (r = 0.56, p < 0.001). High SIP1 expression was associated with a lower survival rate among ACC cases (p < 0.05).
Vimentin, TWIST1, and SIP1 expressions are increased in aggressive ACT. Therefore, EMT may play a relevant role in adrenal tumorigenesis.
上皮-间充质转化（EMT）是一种生物学动态过程，在此过程中上皮细胞失去上皮表型，获得间充质浸润和迁移特性。这被认为是癌症进展和转移的一个重要步骤。尽管这在其他肿瘤中已有详细描述，但 EMT 在肾上腺皮质肿瘤（ACT）中的作用尚未得到解决。
本研究旨在评估 EMT 标志物 E-钙黏蛋白、波形蛋白和纤维连接蛋白，以及 EMT 转录因子（EMT-TFs）TWIST1、SIP1 和 SNAIL 在 24 例肾上腺皮质癌（ACC）、19 例肾上腺皮质腺瘤（ACA）、27 例儿童期起病的肾上腺皮质肿瘤（CAT）和 12 例正常肾上腺组织中的表达。还评估了 EMT 和 EMT-TFs 与临床结局和病理特征的关系。
与 ACC、ACA 和正常肾上腺组织相比，CAT 样本中细胞质波形蛋白的表达增加（p<0.001）。各组间 E-钙黏蛋白和纤维连接蛋白的表达无差异。TWIST1 和 SIP1 的核和细胞质表达在 CAT 和 ACC 与 ACA 和正常组织样本中更强（均 p<0.05）。与正常组织相比，无论分类如何，ACT 均表现出 SNAIL 表达增加（p<0.05）。在 vimentin 和 TWIST1 之间（r=0.44，p<0.001）、SIP1（r=0.51，p<0.001）和 SNAIL（r=0.23，p<0.05）之间观察到显著相关性。TWIST1 和 SIP1 的表达呈显著相关性（r=0.56，p<0.001）。SIP1 高表达与 ACC 病例生存率降低相关（p<0.05）。
侵袭性 ACT 中波形蛋白、TWIST1 和 SIP1 的表达增加。因此，EMT 可能在肾上腺肿瘤发生中发挥相关作用。
