Takano T, Ito Y, Hirokawa M, Yoshida H, Miyauchi A
Department of Laboratory Medicine, Osaka University Graduate School of Medicine, D2, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Br J Cancer. 2007 May 21;96(10):1549-53. doi: 10.1038/sj.bjc.6603764. Epub 2007 Apr 24.
Frequency of a BRAF V600E mutation in anaplastic thyroid carcinoma, which is thought to be derived mainly from papillary carcinoma by multi-step carcinogenesis, is much lower than that in papillary carcinomas. To clarify this phenomenon, we analysed BRAF V600E mutation in 20 cases of anaplastic carcinoma and 13 accompanying differentiated carcinomas. Among twenty cases of anaplastic carcinomas, nine and four accompanied papillary and follicular carcinomas, respectively. BRAF V600E mutation was found in four (20%) cases. BRAF V600E mutation was found in three of nine (33.3%), none of four and one of seven (14.3%) anaplastic carcinomas with papillary carcinoma, follicular carcinoma and without differentiated components, respectively. All three papillary carcinomas accompanied by anaplastic carcinoma with a BRAF V600E mutation were also shown to have a BRAF V600E mutation. In summary, BRAF V600E mutation was occasionally observed in anaplastic carcinomas with papillary carcinoma, and the low frequency of BRAF V600E mutation in anaplastic carcinoma was thought to be due to the low frequency of anaplastic carcinomas with papillary carcinoma. These findings raise a question about the classical model of anaplastic transformation and suggest some roles of thyroid cancer stem cells in the generation of anaplastic carcinoma.
间变性甲状腺癌被认为主要通过多步骤癌变过程由乳头状癌演变而来，其BRAF V600E突变的频率远低于乳头状癌。为阐明这一现象，我们分析了20例间变性癌及13例伴发的分化型癌中的BRAF V600E突变情况。在20例间变性癌中，分别有9例和4例伴发乳头状癌和滤泡状癌。4例（20%）发现有BRAF V600E突变。在伴发乳头状癌、滤泡状癌及无分化成分的间变性癌中，BRAF V600E突变分别在9例中的3例（33.3%）、4例中的0例以及7例中的1例（14.3%）被发现。所有3例伴发有BRAF V600E突变的间变性癌的乳头状癌也都显示存在BRAF V600E突变。总之，在伴发乳头状癌的间变性癌中偶尔可观察到BRAF V600E突变，间变性癌中BRAF V600E突变频率较低被认为是由于伴发乳头状癌的间变性癌频率较低所致。这些发现对间变性转化的经典模型提出了疑问，并提示甲状腺癌干细胞在间变性癌发生过程中可能发挥一定作用。
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