Jung Chang Won, Han Kang Hee, Seol Hyesil, Park Sunhoo, Koh Jae Soo, Lee Seung-Sook, Kim Min Joo, Choi Ik Joon, Myung Jae Kyung
Department of Pathology, Korea Cancer Center Hospital Seoul, Korea.
Department of Pathology, Korea Cancer Center Hospital Seoul, Korea ; Laboratory of Radiation Pathology, Korea Cancer Center Hospital Seoul, Korea.
Int J Clin Exp Pathol. 2015 Jan 1;8(1):560-8. eCollection 2015.
Anaplastic thyroid carcinoma (ATC) is an undifferentiated tumor of the thyroid that has poor prognosis owing to its aggressive behavior and resistance to current treatments. We hypothesized that the stem cell properties induced by the epithelial-mesenchymal transition (EMT) was one of reasons for the dismal outcome of ATC.
Paraffin blocks and slides of 17 ATC cases were retrieved. We also collected 60 cases of papillary thyroid carcinoma (PTC) for comparison. We used immunohistochemistry to examine the expression of multiple markers of cancer stem cells and EMT-activating transcriptional factors.
Majority of ATC cases showed loss of epithelial (E)-cadherin expression (15/17); however, all PTC cases (60/60) retained E-cadherin expression. EMT-activating transcription factors, such as snail and slug, were more frequently expressed in ATC than PTC cases (35.3% versus 6.7%, 76.5% versus 5%, respectively). Cancer stem cell markers such as CD133 and nestin were more highly expressed in ATC than PTC (52.9% versus 5%, 52.9% versus 0%, respectively).
We found that the expression of EMT-related factors and stem cell markers was higher in ATC than PTC. We therefore conclude that stemness induced by EMT plays an important role in the pathogenesis of ATC.
间变性甲状腺癌(ATC)是一种甲状腺未分化肿瘤,因其侵袭性生物学行为和对现有治疗的抵抗性而预后较差。我们推测,上皮-间质转化(EMT)诱导的干细胞特性是ATC预后不良的原因之一。
收集17例ATC病例的石蜡块和切片。我们还收集了60例甲状腺乳头状癌(PTC)病例用于比较。我们采用免疫组织化学法检测癌干细胞和EMT激活转录因子多种标志物的表达。
大多数ATC病例显示上皮型(E)-钙黏蛋白表达缺失(15/17);然而,所有PTC病例(60/60)均保留E-钙黏蛋白表达。EMT激活转录因子,如蜗牛蛋白和蛞蝓蛋白,在ATC病例中的表达频率高于PTC病例(分别为35.3%对6.7%,76.5%对5%)。癌干细胞标志物如CD133和巢蛋白在ATC中的表达高于PTC(分别为52.9%对5%,52.9%对0%)。
我们发现EMT相关因子和干细胞标志物在ATC中的表达高于PTC。因此,我们得出结论,EMT诱导的干性在ATC发病机制中起重要作用。