PDF(Pubmed)
Abstract：
Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD-L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.
摘要：
间变性甲状腺癌（ATC）是最晚期和侵袭性甲状腺癌，低分化甲状腺癌（PDTC）缺乏间变性组织学，但已失去结构和细胞学分化。只有少数研究集中在两种晚期癌和共存的分化型甲状腺癌（DTC）之间的遗传关系上。在本研究中,我们调查了57个ATC和PDTC样本的临床病理特征和遗传特征，其中33例合并有DTC成分或DTC病史。我们对BRAFV600E进行了免疫组织化学，p53和PD-L1表达，TERT启动子和RAS突变的Sanger测序，ALK和RET重排的荧光原位杂交。我们发现ATCs和PDTC与其共存的DTC共享相似的基因改变，大多数DTC是携带频繁TERT启动子突变的侵袭性亚型。与共存的DTC相比，ATC表达p53和PD-L1的比例明显更高，而表达PAX-8和TTF-1的比例较低。我们的研究结果提供了更可靠的证据，证明ATCs和PDTC源自DTC。
