The prevalence and prognostic value of BRAF mutation in thyroid cancer
The prevalence and prognostic value of BRAF mutation in thyroid cancer
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DOI：
10.1097/sla.0b013e318148563d
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发表时间：
2007-09-01
影响因子：
9
通讯作者：
Griffin, Ann
中科院分区：
文献类型：
--
作者：
Kebebew, Electron;Weng, Julie;Griffin, Ann
目的：检测BRAF基因突变在甲状腺癌组织学亚型中的发生率，并确定BRAF基因突变与甲状腺乳头状癌预后不良指标和患者预后的关系。甲状腺癌分子生物学的进展有助于确定疾病侵袭性的候选标记物。一种常见的基因突变是BRAF癌基因(BRAF V600E)的点突变，该突变主要见于乳头状甲状腺癌，与更具侵袭性的疾病相关。方法：对314例甲状腺癌(245例常规乳头状癌、73例滤泡性甲状腺癌和29例滤泡型乳头状癌)的347例肿瘤标本进行BRAF V600E突变检测。结果：BRAF V600E突变在常规甲状腺乳头状癌中的发生率(51.0%)高于滤泡型乳头状癌(24.1%)和滤泡型甲状腺癌(1.4%)(P<；0.0001)。在传统乳头状甲状腺癌患者中，BRAF V600E突变与年龄(P=0.0381)、淋巴结转移(P=0.0323)、远处转移(P=0.045)、较高的TNM分期(I和II期与III和IV期，P=0.0389)、复发和持续性疾病(P=0.009)有关，中位随访时间为6.0年。多因素分析显示，BRAF V600E突变[OR(95%CI)=4.2(1.2~14.6)]和淋巴结转移[OR(95%CI)=7.75(2.1~28.5)]与传统乳头状甲状腺癌患者的复发和持续性疾病独立相关。在传统的乳头状甲状腺癌患者中，它与侵袭性肿瘤表型和较高的复发和持续性疾病风险有关。对这种突变的检测可能对选择初始治疗和后续监测有用。
Objective: To examine the prevalence of BRAF mutation among thyroid cancer histologic subtypes and determine the association of BRAF mutation with indicators of poor prognosis for papillary thyroid cancer and patient outcome.Summary Background Data: The appropriate extent of surgical treatment, adjuvant therapy and follow-up monitoring for thyroid cancer remains controversial. Advances in the molecular biology of thyroid cancer have helped to identify candidate markers of disease aggressiveness. A commonly found genetic alternation is a point mutation in the BRAF oncogene (BRAF V600E), which is primarily found in papillary thyroid cancer and is associated with more aggressive disease.Methods: BRAF V600E mutation status was determined in 347 tumor samples from 314 patients with thyroid cancer (245 with conventional papillary thyroid cancer, 73 with follicular thyroid cancer, and 29 with the follicular variant of papillary thyroid cancer). Univariate and multivariate analyses were performed to determine the association of BRAF V600E with clinicopathologic factors and patient outcome.Results: The prevalence of BRAF V600E mutation was higher in conventional papillary thyroid cancer (51.0%) than in follicular variant of papillary thyroid cancer (24.1%) and follicular thyroid cancer (1.4%) (P < 0.0001). In patients with conventional papillary thyroid cancer, BRAF V600E mutation was associated with older age (P = 0.0381), lymph node metastasis (P = 0.0323), distant metastasis (P = 0.045), higher TNM stage (I and II vs. III and IV, P = 0.0389), and recurrent and persistent disease (P = 0.009) with a median follow-up time of 6.0 years. Multivariate analysis showed that BRAF V600E mutation [OR (95% CI) = 4.2 (1.2-14.6)] and lymph node metastasis [OR (95% Cl) = 7.75 (2.1-28.5)] were independently associated with recurrent and persistent disease in patients with conventional papillary thyroid cancer.Conclusions: BRAF V600E mutation is primarily present in conventional papillary thyroid cancer. It is associated with an aggressive tumor phenotype and higher risk of recurrent and persistent disease in patients with conventional papillary thyroid cancer. Testing for this mutation may be useful for selecting initial therapy and for follow-up monitoring.