Wang Yangang, Ji Meiju, Wang Wei, Miao Zhimin, Hou Peng, Chen Xinyan, Xu Feng, Zhu Guangwu, Sun Xianlu, Li Yujun, Condouris Steven, Liu Dingxie, Yan Shengli, Pan Jie, Xing Mingzhao
Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Endocr Relat Cancer. 2008 Mar;15(1):183-90. doi: 10.1677/ERC-07-0182.
The relationship among BRAF mutation, platelet counts, and platelet-derived growth factor (PDGF) with respect to clinicopathological outcomes of papillary thyroid cancer (PTC) may play a role in PTC pathogenesis but remains undefined. We examined the T1799A BRAF mutation by direct genomic DNA sequencing in 108 primary PTC samples from a Chinese cohort and analyzed its relationship with clinicopathological, hematological, and other laboratory results as well as the levels of expression of PDGF in tumors. We found that the BRAF mutation was significantly associated with extrathyroidal invasion and advanced tumor stages III and IV. Specifically, extrathyroidal invasion was seen in 30/54 (56%) PTC with BRAF mutation versus 18/54 (33%) PTC without the mutation (P=0.02). Tumor stages III and IV were seen in 16/54 (30%) PTC with BRAF mutation versus 7/54 (13%) PTC without the mutation (P=0.04). The BRAF mutation was also significantly associated with a higher platelet count, with 249.28+/-53.76 x 10(9)/l in the group of patients with BRAF mutation versus 207.79+/-58.98 x 10(9)/l in the group without the mutation (P=0.001). An association of higher platelet accounts with extrathyroidal invasion was also seen, with 242.66+/-51.85 x 10(9)/l in patients with extrathyroidal invasion versus 218.49+/-59.10 x 10(9)/l in patients without extrathyroidal invasion (P=0.03). The BRAF T1799A-positive PTC tissues harbored a significantly higher level of PDGF-B than BRAF T1799A-negative PTC tissues. The data suggest that the BRAF T1799A mutation is associated with aggressive pathological outcomes of PTC in which high platelet counts and increased PDGF production may play a role.
BRAF突变、血小板计数和血小板衍生生长因子（PDGF）与甲状腺乳头状癌（PTC）临床病理结果之间的关系可能在PTC发病机制中起作用，但仍不明确。我们通过直接基因组DNA测序检测了来自中国队列的108例原发性PTC样本中的T1799A BRAF突变，并分析了其与临床病理、血液学和其他实验室结果以及肿瘤中PDGF表达水平的关系。我们发现BRAF突变与甲状腺外侵犯及肿瘤晚期III期和IV期显著相关。具体而言，54例BRAF突变的PTC中有30例（56%）出现甲状腺外侵犯，而54例无该突变的PTC中有18例（33%）出现甲状腺外侵犯（P=0.02）。54例BRAF突变的PTC中有16例（30%）处于肿瘤III期和IV期，而54例无该突变的PTC中有7例（13%）处于该阶段（P=0.04）。BRAF突变还与较高的血小板计数显著相关，BRAF突变组患者的血小板计数为249.28±53.76×10⁹/L，而无突变组为207.79±58.98×10⁹/L（P=0.001）。较高的血小板计数与甲状腺外侵犯之间也存在关联，有甲状腺外侵犯的患者血小板计数为242.66±51.85×10⁹/L，无甲状腺外侵犯的患者为218.49±59.10×10⁹/L（P=0.03）。BRAF T1799A阳性的PTC组织中PDGF-B水平明显高于BRAF T1799A阴性的PTC组织。数据表明，BRAF T1799A突变与PTC的侵袭性病理结果相关，其中血小板计数高和PDGF产生增加可能起作用。
