Mutations of the TP53 tumor suppressor gene are highly prevalent in thyroid anaplastic carcinomas (AC) but are also reported in some well-differentiated cancers and even in benign adenomas. The natural history of TP53-mutant adenomas and whether they may represent a precursor for well-differentiated cancer or AC is largely unknown. Similarly, the frequency of TP53 mutations in thyroid nodules found on routine molecular analysis of fine-needle aspiration (FNA) samples is not established. A database on 44,510 FNA samples from thyroid nodules with predominantly indeterminate cytology tested using ThyroSeq v3 was reviewed to identify TP53-mutant cases and analyze their genetic profile and available clinicopathological findings. Among 260 (0.6%) selected thyroid nodules, 36 had an isolated TP53 mutation and 224 carried a combination of TP53 with other genetic alterations. No significant difference was observed between these groups with respect to patient age, gender, nodule size, and spectrum of TP53 mutations. Histopathologically, 86% of the resected nodules with isolated TP53 mutations were benign (mostly adenomas), whereas 82% of nodules carrying TP53 mutations co-occurring with other alterations were cancers (P = 0.001), including de-differentiated AC. TP53-mutant benign tumors and well-differentiated cancers often had scattered single neoplastic cells with bizarre nuclei resembling those comprising AC. Our study demonstrates that a small but distinct proportion of thyroid nodules carry a TP53 mutation, either as a single genetic event or in combination with other alterations. While the latter is mostly cancers prone to dedifferentiation, there is at least a theoretical possibility that TP53-mutated adenomas may represent a precursor for such cancers, including AC.

中文翻译：

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TP53突变滤泡性腺瘤可以是甲状腺未分化癌的前兆吗？

TP53 肿瘤抑制基因的突变在甲状腺间变性癌 (AC) 中非常普遍，但在一些分化良好的癌症甚至良性腺瘤中也有报道。TP53 突变腺瘤的自然史以及它们是否可能代表分化良好的癌症或 AC 的前兆在很大程度上是未知的。同样，在细针抽吸 (FNA) 样本的常规分子分析中发现的甲状腺结节中 TP53 突变的频率也未确定。回顾了使用 ThyroSeq v3 检测的来自甲状腺结节的 44,510 个 FNA 样本的数据库，这些样本主要是不确定的细胞学，以确定 TP53 突变病例并分析其遗传谱和可用的临床病理学发现。在 260 个 (0.6%) 选定的甲状腺结节中，36 人有一个孤立的 TP53 突变，224 人携带 TP53 与其他遗传改变的组合。在患者年龄、性别、结节大小和 TP53 突变谱方面，这些组之间没有观察到显着差异。组织病理学上，86% 的具有孤立 TP53 突变的切除结节是良性的（主要是腺瘤），而 82% 的携带 TP53 突变与其他改变同时发生的结节是癌症（P = 0.001），包括去分化的 AC。TP53 突变的良性肿瘤和分化良好的癌症通常具有散在的单个肿瘤细胞，其具有类似于包含 AC 的奇异细胞核。我们的研究表明，一小部分但不同的甲状腺结节携带 TP53 突变，无论是作为单一遗传事件还是与其他改变相结合。