Liu Jing, Brown Robert E
Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston Medical School Houston, Texas 77030, USA.
Int J Clin Exp Pathol. 2010 Oct 1;3(8):755-62.
Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm resistant to radiation and chemotherapy. Epithelial-mesenchymal transition (EMT) generating cells with stem cell characteristics have been reported to be associated with chemoradioresistance in cultured cells. However, EMT and stem cell properties in ATC have not been fully investigated. In this study, we retrieved 2 thyroidectomy specimens of ATC with coexisting well differentiated thyroid carcinomas (DTCs) including one papillary carcinoma (PTC) and one follicular carcinoma (FTC). We used im-munohistochemistry to examine the expression of stem cell markers (nestin, CD133 and CD44) and a marker for EMT (E-cadherin). Intense expressions of nestin, CD133 and CD44, and no expression of E-cadherin were observed in both ATCs. In contrast, the PTC and FTC, and non-neoplastic thyroid tissue in both cases were negative for nestin and positive for E-cadherin. The expressions of CD133 and CD44 were variable in the PTC, FTC, and non-neoplastic thyroid tissue and were at a lower level of expression of these markers in the overall pattern. The results confirmed EMT, demonstrated the stem cell phenotype in ATC, and revealed the difference in expression of these markers between ATC and DTCs/non-neoplastic thyroid tissue. Nestin may be the most specific marker for stemness in ATC by immuno-histochemial staining. The results warrant future studies on a large series of cases in order to gain the understanding of the tumor biology and to provide molecular basis for restoring the sensitivities to clinical therapies.
间变性甲状腺癌(ATC)是一种对放疗和化疗具有高度抗性的侵袭性肿瘤。据报道,具有干细胞特征的上皮-间质转化(EMT)所产生的细胞与培养细胞中的放化疗抗性有关。然而,ATC中的EMT和干细胞特性尚未得到充分研究。在本研究中,我们获取了2例合并存在高分化甲状腺癌(DTC)的ATC甲状腺切除标本,其中1例为乳头状癌(PTC),1例为滤泡状癌(FTC)。我们采用免疫组织化学法检测干细胞标志物(巢蛋白、CD133和CD44)以及EMT标志物(E-钙黏蛋白)的表达情况。在这2例ATC中均观察到巢蛋白、CD133和CD44的强表达,而E-钙黏蛋白无表达。相比之下,2例中的PTC、FTC以及非肿瘤性甲状腺组织巢蛋白呈阴性,E-钙黏蛋白呈阳性。CD133和CD44在PTC、FTC及非肿瘤性甲状腺组织中的表达情况各不相同,总体上这些标志物的表达水平较低。结果证实了ATC中存在EMT,证明了其干细胞表型,并揭示了这些标志物在ATC与DTC/非肿瘤性甲状腺组织之间的表达差异。通过免疫组织化学染色,巢蛋白可能是ATC中干性最特异的标志物。这些结果为今后开展大量病例研究以深入了解肿瘤生物学特性并为恢复临床治疗敏感性提供分子基础提供了依据。