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BRAF(V600E)突变对甲状腺乳头状癌中钠/碘同向转运体表达的影响。

Effects of BRAF(V600E) mutation on Na(+)/I(-) symporter expression in papillary thyroid carcinoma.

作者信息

Dong Hong, Shen Wen-Zhuang, Yan Yu-Jing, Yi Ji-Lin, Zhang Lin

机构信息

Department of Thyroid and Breast Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Wuhan, 430030, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2016 Feb;36(1):77-81. doi: 10.1007/s11596-016-1545-3. Epub 2016 Feb 3.

Abstract

Radioiodine ablation (RIA) therapy is one of the most important treatments for papillary thyroid carcinoma (PTC), but some patients who received (131)I have radioiodine-refractory disease caused by the decreased expression of the Na(+)/I(-) symporter (NIS). BRAF(V600E) mutation is one possible risk factor that can disturb the NIS expression, but the roles are unclear in clinical practice. This research discussed the association of BRAF(V600E) mutation and NIS expression in PTC tissue and the clinical implications in RIA therapy. 134 PTC samples were collected between June 2013 and June 2014 from Tongji Hospital affiliated to Tongji Medical College, and their clinical characteristics were analyzed. RT-PCR was used to detect the BRAF(V600E) mutation from formalin-fixed paraffin-embedded samples, and immunohistochemistry was applied to detect the NIS expression. IPP software was used to calculate the relative expression quantity of NIS. We found that there was no significant correlation between the absorbance (A) values of NIS and clinicopathologic features in these cases, even thyroid stimulating hormone. BRAF(V600E) mutation showed inhibitory effect on the NIS expression without statistically significant difference in all PTC cases (β=-0.0195, P=0.085), but in the subgroup without hashimoto's thyroiditis (HT), BRAF(V600E) mutation could significantly inhibit the NIS expression (β=-0.0257, P=0.046). The results indicate that BRAF(V600E) mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.

摘要

放射性碘消融(RIA)治疗是甲状腺乳头状癌(PTC)最重要的治疗方法之一,但一些接受过(131)I治疗的患者会因钠/碘同向转运体(NIS)表达降低而出现放射性碘难治性疾病。BRAF(V600E)突变是一个可能干扰NIS表达的风险因素,但在临床实践中的作用尚不清楚。本研究探讨了BRAF(V600E)突变与PTC组织中NIS表达的相关性及其在RIA治疗中的临床意义。2013年6月至2014年6月期间从同济医学院附属同济医院收集了134例PTC样本,并分析了其临床特征。采用逆转录-聚合酶链反应(RT-PCR)从福尔马林固定石蜡包埋样本中检测BRAF(V600E)突变,应用免疫组织化学检测NIS表达。使用IPP软件计算NIS的相对表达量。我们发现,在这些病例中,NIS的吸光度(A)值与临床病理特征之间无显著相关性,即使是促甲状腺激素。BRAF(V600E)突变对所有PTC病例的NIS表达均有抑制作用,但差异无统计学意义(β=-0.0195,P=0.085),但在无桥本甲状腺炎(HT)的亚组中,BRAF(V600E)突变可显著抑制NIS表达(β=-0.0257,P=0.046)。结果表明,BRAF(V600E)突变与无HT的PTC中NIS表达降低相关,提示这些患者在RIA治疗期间存在放射性碘难治性效应。

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