Expression of epithelial-mesenchymal transition regulators TWIST, SLUG and SNAIL in follicular thyroid tumours may relate to widely invasive, poorly differentiated and distant metastasis

Expression of epithelial-mesenchymal transition regulators TWIST, SLUG and SNAIL in follicular thyroid tumours may relate to widely invasive, poorly differentiated and distant metastasis
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DOI:
10.1111/his.13778
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发表时间:
2019-04-01
期刊:
影响因子:
6.4
通讯作者:
Sun, Baocun
Sun, Baocun
中科院分区:
医学2区
文献类型:
--
作者:
Wu, Jianghua;Zhang, Yanhui;Sun, Baocun

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目的评估上皮间质转化(EMT)调节因子在滤泡性甲状腺肿瘤中的表达。方法与结果应用免疫组织化学方法检测18例滤泡性腺瘤(FA)、12例微创滤泡性甲状腺癌(MI-FTC)、16例广泛浸润滤泡性甲状腺癌(WI-FTC)、14例正常甲状腺组织中E-cadherin(E-CAD)及转录因子TWIST、SLUG和SNAIL的表达。10例低分化滤泡状甲状腺癌(PDTC)和6例未分化甲状腺癌(ATC)。还检查了其中6例转移性肿瘤组织。结果显示,在一组滤泡性肿瘤病例中,EMT调节因子的表达呈增加趋势,这些病例具有从低风险到高风险恶性肿瘤的一系列形态亚型。EMT调节因子在WI-FTC、PDTC和ATC组中表达较高,而在FA和MI-FTC组中表达较低。E-CAD和EMT调节因子在肿瘤中心和浸润前沿(IF)的表达强度不同。E-CAD的丢失和EMT调节因子的表达与高分化滤泡癌(WD-FTC)的远处转移和血管浸润(VI)显著相关,并且6个转移部位的肿瘤也显示EMT调节因子阳性的变量。无病生存分析显示,在WD-FTC中EMT调节因子的表达与肿瘤无病结局之间存在明显的相关性。结论本研究支持EMT在甲状腺滤泡癌发生发展中的作用,提示EMT调控蛋白在广泛侵袭和远处转移的WD-FTC中可能起重要作用。
Aims To assess the expression of epithelial-mesenchymal transition (EMT) regulators in follicular thyroid tumours. Methods and results The expression of E-cadherin (E-CAD) and transcription factors TWIST, SLUG and SNAIL in follicular thyroid tumours was examined by immunohistochemistry in tissue samples, including 18 follicular adenomas (FA), 12 minimally invasive follicular thyroid carcinomas (MI-FTC), 16 widely invasive follicular thyroid carcinomas (WI-FTC), 10 poorly differentiated follicular thyroid carcinomas (PDTC) and six anaplastic thyroid carcinomas (ATC). Metastatic tumour tissues from six of these cases were also examined. The results showed an increasing expression trend of EMT regulators in a panel of follicular tumour cases with a spectrum of morphological subtypes from low- to high-risk malignancy. The expression of EMT regulators was higher in the WI-FTC, PDTC and ATC groups but focal and lower in the FA and MI-FTC groups. Different expression intensity of E-CAD and EMT regulators at the tumour centre part and the invasive front (IF) was observed. The loss of E-CAD and expression of EMT regulators was significantly correlated with distant metastasis and vascular invasion (VI) in the well-differentiated follicular carcinoma (WD-FTC), and six tumours of metastatic sites also showed variables positive for EMT regulators. The disease-free survival analysis showed an apparent relationship between the expression of EMT regulators and the tumour disease-free outcomes in WD-FTC. Conclusions Our study supported the role of EMT in the development of follicular thyroid carcinoma and indicated that EMT regulatory proteins may play an important role in WD-FTC that are widely invasive and exhibit distant metastasis.