High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes
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DOI：
10.1002/cncr.24118
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发表时间：
2009-03-01
期刊：
影响因子：
6.2
通讯作者：
Cerutti, Janete M.
中科院分区：
文献类型：
--
作者：
Oler, Gisele;Cerutti, Janete M.
背景技术背景：虽然一些研究无疑表明BRAF突变是甲状腺乳头状癌（PTC）发病机制中的重要遗传事件，但其预后意义及其与低分化状态的相关性仍不清楚。有人认为，这种差异可能至少部分是由于分析的病例数量不足、流行病学因素以及这些研究中包含的PTC不同变体的组合。方法：在此背景下，首先评估了巴西PTC队列（n = 120）中BRAF突变的患病率，并将其与临床病理特征相关联。通过直接测序评估BRAF外显子15突变。此外，使用定量聚合酶链反应，碘代谢基因（NIS和TSHR）的表达水平是否与BRAF突变状态相关的问题进行了研究。结果：在PTC病例中发现BRAF突变的高患病率（48%）。BRAF突变被发现与PTC的经典变异显著相关（66%; P <0.0001），尽管它也被发现在滤泡变异中（21%）。亚型分层表明BRAF V600 E突变与PTC经典变异患者的肿瘤大小、甲状腺外浸润、淋巴结转移和疾病复发风险以及死亡率相关。此外，NIS和TSHR的表达水平在携带BRAF V600 E突变的PTC中显著降低。结论：这些发现提供了进一步的证据，BRAF可能与更积极的表型和低分化状态，由于碘代谢基因的表达减少。在目前的研究人群中寻找BRAF突变似乎对预测PTC患者的预后和指导治疗有价值。Cancer 2009;115：972-80. (c)2009年美国癌症协会。
BACKGROUND: Although several studies undoubtedly demonstrated that BRAF mutation is an important genetic event in the pathogenesis of papillary thyroid carcinoma (PTC), its prognostic significance and correlation with less differentiated states remains unclear. It has been suggested that the discrepancy may be at least partially due to the insufficient number of cases analyzed, epidemiologic factors, and a combination of different variants of PTC included in these studies. METHODS: In this context, the prevalence of the BRAF mutation in a Brazilian cohort of PTCs (n = 120) was first assessed and correlated with clinicopathologic features. The BRAF exon 15 mutation was evaluated by direct sequencing. Furthermore, using quantitative polymerase chain reaction, the issue of whether the expression level of the iodide-metabolizing genes (NIS and TSHR) was correlated with BRAF mutational status was investigated. RESULTS: A high prevalence of the BRAF mutation was found in PTC cases (48%). The BRAF mutation was found to be significantly associated with the classic variant of PTC (66%; P < .0001), although it was found in the follicular variant as well (21%). Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC. Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs harboring the BRAF V600E mutation. CONCLUSIONS: These findings provide further evidence that BRAF might be associated with a more aggressive phenotype and less differentiated state due to decreased expression of iodide-metabolizing genes. The search for a BRAF mutation in the current study population appears to be valuable for predicting prognosis and guiding management in patients with PTC. Cancer 2009;115:972-80. (c) 2009 American Cancer Society.