Department of Pathology, Hôpital Central, CHU, Nancy, France.
Pathology. 2011 Aug;43(5):447-52. doi: 10.1097/PAT.0b013e3283486178.
The aim of this study was to genotype a series of papillary thyroid carcinomas (PTCs) and anaplastic thyroid carcinomas (ATCs) for BRAF mutation, and to evaluate p53 and SOX2 expression as factors implicated in tumour progression.
The study included 17 PTCs and 14 ATCs. Analysis of the exon 15 of BRAF was based on direct sequencing. Immunohistochemistry was used to evaluate p53 and SOX2 expression.
V600E (c.1799T>A) mutation was observed in 53% (9/17) of PTCs. Two cases of ATCs (2/14; 14%), both with PTC component, harboured BRAF mutation: the classical V600E mutation and an undocumented duplication of codon 599 (c.1795_1797dup; p.Thr599dup). These mutations were present in ATC as well as PTC tumour cells. Overexpression of p53 and SOX2 was depicted respectively in 64% (9/14) and 29% (4/14) of ATCs, and absent in PTCs.
We confirm that V600E mutation is a frequent and specific event in PTC. BRAF-mutated ATCs are associated with a PTC component displaying the same mutation. We describe a new mutation of BRAF, T599dup, in a case of ATC with tall cell PTC component. Moreover, progression from PTC to ATC could be favoured by further TP53 mutation and SOX2 expression.
本研究旨在对一系列甲状腺乳头状癌（PTC）和间变性甲状腺癌（ATC）进行 BRAF 突变基因分型，并评估 p53 和 SOX2 表达作为肿瘤进展相关的因素。
本研究纳入了 17 例 PTC 和 14 例 ATC。BRAF 外显子 15 的分析基于直接测序。采用免疫组织化学法评估 p53 和 SOX2 的表达。
53%（9/17）的 PTC 存在 V600E（c.1799T>A）突变。2 例（2/14；14%）伴有 PTC 成分的 ATC 存在 BRAF 突变：经典的 V600E 突变和未记录的密码子 599 重复（c.1795_1797dup；p.Thr599dup）。这些突变存在于 ATC 和 PTC 肿瘤细胞中。p53 和 SOX2 的过表达分别在 64%（9/14）和 29%（4/14）的 ATC 中被描绘，而在 PTC 中不存在。
我们证实 V600E 突变是 PTC 中常见且特异的事件。BRAF 突变型 ATC 与具有相同突变的 PTC 成分相关。我们描述了一种新的 BRAF 突变，T599dup，在一例具有高细胞 PTC 成分的 ATC 中。此外，PTC 向 ATC 的进展可能受到 TP53 突变和 SOX2 表达的进一步促进。
