Influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer
Influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer
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DOI：
10.1210/jc.2005-2836
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发表时间：
2006-09-01
影响因子：
5.8
通讯作者：
Shong, Minho
中科院分区：
文献类型：
--
作者：
Jo, Young Suk;Li, Shengjin;Shong, Minho
内容：BRAF突变可能影响与甲状腺癌发生和发展相关的分子标志物的表达模式。目的：本研究的目的是探讨BRAF V600 E突变对甲状腺乳头状癌（PTC）中半乳糖凝集素-3、环氧合酶-2、细胞周期蛋白D1、p53和血管内皮生长因子（VEGF）表达的影响。回顾性分析163例PTC和28例结节性增生患者。结果：161例PTC患者中，BRAF V600 E（+）102例（63.4%），与V600 E（-）59例（36.6%）相比，BRAF V600 E（+）患者肿瘤体积明显增大（P = 0.01）。虽然PTC组织中所选分子标记物的表达水平高于结节性增生组织，但BRAF V600 E（+）PTC中的几种分子标记物的表达水平与BRAF V600 E（-）PTC中的表达水平无显著差异。但VEGF在BRAF V600 E（+）PTC中的表达较BRAF V600 E（-）PTC明显上调。VEGF表达水平与肿瘤大小（P < 0.001）、甲状腺外浸润（P = 0.02）和肿瘤分期（P = 0.04）呈显著正相关。多因素分析显示VEGF在BRAF V600 E（+）PTC中表达上调（OR 2.5，可信区间1.1-5.6; P = 0.03）。VEGF的表达水平与肿瘤大小、甲状腺外浸润和分期密切相关。VEGF表达水平相对较高可能与BRAF V600 E（+）PTC的临床结局较差和复发有关。
Context: The BRAF mutation may influence the expression patterns of molecular markers that are related to the development and progression of thyroid cancer.Objective: The objective of the study was to investigate the effects of the BRAF V600E mutation on expression of galectin-3, cyclooxygenase-2, cyclin D1, p53, and vascular endothelial growth factor (VEGF) in papillary thyroid cancer (PTC).Design, Setting, and Subjects: One hundred sixty-three PTC and 28 nodular hyperplasia patients were selected retrospectively. The presence of the BRAF V600E mutation and the level of expression of the molecular markers were determined.Results: Of 161 PTC patients, 102 patients (63.4%) were BRAF V600E(+), and these cases had significantly larger tumor sizes (P = 0.01), compared with V600E(-) cases (n = 59, 36.6%). Although PTC tissues had higher expression levels of the selected molecular markers than nodular hyperplasia tissues, expression levels of several molecular markers in BRAF V600E(+) PTC were not significantly different from those of BRAF V600E(-) PTC. But VEGF was significantly up-regulated in BRAF V600E(+) PTC, compared with BRAF V600E(-) PTC. VEGF expression levels were strongly positively correlated to tumor size (P < 0.001), extrathyroidal invasion (P = 0.02), and tumor stage (P = 0.04). Multivariate analysis clearly showed that VEGF expression was up-regulated in BRAF V600E(+) PTC (odds ratio 2.5, confidence interval 1.1-5.6; P = 0.03).Conclusions: BRAF V600E(+) PTC tended to have larger tumor volumes and higher expression of VEGF. The level of VEGF expression was closely correlated with tumor size, extrathyroidal invasion, and stage. The relatively high levels of VEGF expression may be related to poorer clinical outcomes and recurrences in BRAF V600E(+) PTC.