Lymphatic mapping establishes the role of BRAF gene mutation in papillary thyroid carcinoma

Lymphatic mapping establishes the role of BRAF gene mutation in papillary thyroid carcinoma
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DOI:
10.1097/01.sla.0000224751.80858.13
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发表时间:
2006-11-01
期刊:
影响因子:
9
通讯作者:
Hoon, Dave S. B.
Hoon, Dave S. B.
中科院分区:
医学1区
文献类型:
--
作者:
Kim, Joseph;Giuliano, Armando E.;Hoon, Dave S. B.

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目的:目的:明确BRAF基因突变在甲状腺乳头状癌发生发展中的作用。方法:收集甲状腺乳头状癌患者行甲状腺切除术和前哨淋巴结活检的病例。BRAF突变进行了评估,在原发性肿瘤和匹配的前哨淋巴结定量实时PCR assay.Results:组织标本从103个连续的患者进行了评价。原发肿瘤的BRAF突变在34例(33%)患者中检测到。在34例BRAF突变患者中,26例(76%)检测到伴随淋巴结转移。相反,在69例BRAF突变阴性的原发肿瘤患者中,只有12例(17%)患者发生淋巴结转移(χ 2,P < 0.0001)。在与BRAF突变阳性原发性肿瘤匹配的26例淋巴结转移中的20例(77%)中检测到BRAF突变;在与BRAF突变阴性原发性肿瘤匹配的淋巴结转移中未检测到BRAF突变。单因素分析确定年龄、分期、肿瘤大小和BRAF突变是淋巴结转移的预后因素。多因素分析中,仅BRAF突变仍是影响甲状腺乳头状癌淋巴结转移的重要因素(OR = 10.8,95%可信区间,3.5-34.0,P < 0.0001)。该研究表明,该基因突变是局部区域淋巴结转移的一个重要危险因素,并有潜在的效用作为替代标记物。
Objective: To define the role of BRAF gene mutation in the progression of papillary thyroid carcinoma.Summary Background Data: BRAF gene mutation is frequently detected in papillary thyroid carcinoma. Its role in pathogenesis or progression is under investigation.Methods: Patients who underwent thyroidectomy and sentinel lymph node biopsy for papillary thyroid cancer were accrued. BRAF mutation was assessed in primary tumors and matched sentinel lymph nodes by a quantitative real-time PCR assay.Results: Tissue specimens from 103 consecutive patients were evaluated. BRAF mutation of the primary tumor was detected in 34 (33%) patients. In 26 of 34 (76%) patients with BRAF mutation, concomitant lymph node metastasis was detected. On the contrary, in 69 patients with BRAF mutation-negative primary tumors, only 12 (17%) patients had lymph node metastasis (chi(2), P < 0.0001). BRAF mutation was detected in 20 of 26 (77%) lymph node metastases matched to BRAF mutation-positive primary tumors; it was not detected in lymph node metastases matched to BRAF mutation-negative primary tumors. Univariate analysis identified age, stage, tumor size, and BRAF mutation as prognostic factors for lymph node metastasis. In multivariate analysis, only BRAF mutation remained a significant prognostic factor for lymph node metastasis (odds ratio = 10.8, 95% confidence interval, 3.5-34.0, P < 0.0001).Conclusions: BRAF mutation may be a key genetic factor for the metastatic progression of papillary thyroid carcinoma. The study demonstrates that this gene mutation is a significant risk factor for locoregional lymph node metastasis and has potential utility as a surrogate marker.