Durante C, Puxeddu E, Ferretti E, Morisi R, Moretti S, Bruno R, Barbi F, Avenia N, Scipioni A, Verrienti A, Tosi E, Cavaliere A, Gulino A, Filetti S, Russo D
Department of Clinical Sciences, University of Rome La Sapienza, 00161 Rome, Italy.
J Clin Endocrinol Metab. 2007 Jul;92(7):2840-3. doi: 10.1210/jc.2006-2707. Epub 2007 May 8.
BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may influence the prognosis of these tumors.
Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs. DESIGN/SETTING AND PATIENTS: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry.
mRNA levels for all thyroid-specific genes were reduced in all PTCs vs. normal thyroid tissues. NIS, AIT-B, Tg, and TPO expression was significantly lower in BRAF-mut tumors than in the BRAF-wt group. Glut-1 transcript levels were increased in all PTCs, and additional increases were noted in BRAF-mut tumors. In both tumor subsets, the NIS protein that was expressed was abnormally retained in the cytoplasm.
BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism. This effect may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut PTCs.
BRAF突变在甲状腺乳头状癌（PTC）中很常见。通过影响与甲状腺癌发生和分化密切相关的基因表达，它们可能会影响这些肿瘤的预后。
我们的目的是描述PTC中与BRAF突变相关的甲状腺特异性基因的表达情况。
设计/地点和患者：我们检测了56例BRAF突变（BRAF-mut）的PTC和37例BRAF野生型（BRAF-wt）的PTC中甲状腺细胞分化关键标志物的表达。分析了8份正常甲状腺组织样本作为对照。采用定量PCR检测钠/碘同向转运体（NIS）、顶端碘转运体（AIT-B）、甲状腺球蛋白（Tg）、甲状腺过氧化物酶（TPO）、促甲状腺激素受体（TSH-R）、转录因子PAX8和葡萄糖转运体1（Glut1）的mRNA水平。还通过免疫组织化学分析了NIS蛋白的表达和定位。
与正常甲状腺组织相比，所有PTC中所有甲状腺特异性基因的mRNA水平均降低。BRAF-mut肿瘤中NIS、AIT-B、Tg和TPO的表达明显低于BRAF-wt组。所有PTC中Glut-1转录水平均升高，BRAF-mut肿瘤中进一步升高。在两个肿瘤亚组中，表达的NIS蛋白均异常保留在细胞质中。
PTC中的BRAF V600E突变与碘代谢相关关键基因的表达降低有关。这种效应可能会改变放射性碘在BRAF-mut PTC诊断和/或治疗中的有效性。
