Schwertheim S, Sheu S-Y, Worm K, Grabellus F, Schmid K W
Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Horm Metab Res. 2009 Jun;41(6):475-81. doi: 10.1055/s-0029-1215593. Epub 2009 Apr 15.
Poorly differentiated thyroid carcinoma (PDTC) is defined as a malignant follicular cell derived neoplasm, both morphologically and biologically intermediate between well differentiated and anaplastic thyroid carcinoma (ATC). In the present study we investigated the expression levels of two distinct sets of miRNAs ('set 1': miRNA-146b, -181b, -21, -221, -222, all shown to be significantly upregulated in papillary thyroid carcinoma [PTC]; 'set 2': miRNA-30d, -125b, -26a, -30a-5p, and let7c, all downregulated in ATC) in a series of 15 PDTC (including 3 mixed PDTC/PTC), 9 'pure' PTC, and 9 ATC. Compared to normal thyroid tissue all 'set 1' miRNAs were significantly upregulated in PTC (p<0.001); in ATC 4/5 miRNAs were upregulated (p<0.001) whereas in PDTC the expression levels of all 5 miRNAs did not differ significantly from normal thyroid. All miRNAs of 'set 2' were significantly upregulated in PTC (p<0.004) and downregulated in ATC (p<0.03); in PDTC only 3/5 were downregulated (p<0.011). All 10 miRNAs investigated differed significantly (p<0.003) between PTC and PDTC. In the histologically differentiated PTC compound of mixed PDTC/PTC cases, however, miRNA expression levels of all 10 miRNAs investigated lacked significant difference from those found in the PDTC compound, whereas 6/10 miRNAs differed significantly from 'pure' PTC. Our results indicate that analysis of distinct sets of miRNAs represent useful tools to distinguish PDTC from 'pure' PTC. Additionally our findings suggest that lack of deregulation of some miRNAs may select a subset of PTC prone to progression to PDTC.
低分化甲状腺癌(PDTC)被定义为一种源自滤泡细胞的恶性肿瘤,在形态学和生物学上介于高分化甲状腺癌和间变性甲状腺癌(ATC)之间。在本研究中,我们调查了两组不同的微小RNA(miRNA)的表达水平(“第一组”:miRNA-146b、-181b、-21、-221、-222,所有这些在乳头状甲状腺癌[PTC]中均显著上调;“第二组”:miRNA-30d、-125b、-26a、-30a-5p和let7c,所有这些在ATC中均下调),研究对象包括15例PDTC(包括3例混合性PDTC/PTC)、9例“纯”PTC和9例ATC。与正常甲状腺组织相比,所有“第一组”miRNA在PTC中均显著上调(p<0.001);在ATC中,5个miRNA中有4个上调(p<0.001),而在PDTC中,所有5个miRNA的表达水平与正常甲状腺组织无显著差异。“第二组”的所有miRNA在PTC中均显著上调(p<0.004),在ATC中下调(p<0.03);在PDTC中,只有5个中的3个下调(p<0.011)。所研究的全部10个miRNA在PTC和PDTC之间存在显著差异(p<0.003)。然而,在混合性PDTC/PTC病例的组织学高分化PTC成分中,所研究的全部10个miRNA的表达水平与PDTC成分中的表达水平无显著差异,而10个miRNA中有6个与“纯”PTC有显著差异。我们的结果表明,分析不同组的miRNA是区分PDTC和“纯”PTC的有用工具。此外,我们的研究结果表明,某些miRNA缺乏失调可能会选择出一部分易于进展为PDTC的PTC亚群。