Lazar V, Bidart J M, Caillou B, Mahé C, Lacroix L, Filetti S, Schlumberger M
Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France.
J Clin Endocrinol Metab. 1999 Sep;84(9):3228-34. doi: 10.1210/jcem.84.9.5996.
The expression of 4 thyroid tissue-specific genes [Na+/I- symporter (NIS), thyroid peroxidase (TPO), thyroglobulin (Tg), TSH receptor (TSH-R)] as well as of the glucose transporter type 1 (Glut1) gene was analyzed in 90 human thyroid tissues Messenger ribonucleic acids were extracted from 43 thyroid carcinomas (38 papillary and 5 follicular), 24 cold adenomas, 5 Graves' thyroid tissues, 8 toxic adenomas, and 5 hyperplastic thyroid tissues; 5 normal thyroid tissues were used as reference. A kinetic quantitative PCR method, based on the fluorescent TaqMan methodology and real-time measurement of fluorescence, was used. NIS expression was decreased in 40 of 43 thyroid carcinomas (10- to 1200-fold) and in 20 of 24 cold adenomas (2- to 700-fold); it was increased in toxic adenomas and Graves' thyroid tissues (up to 140-fold). TPO expression was decreased in thyroid carcinomas, but was normal in cold adenomas; it was increased in toxic adenomas and Graves' thyroid tissues Tg expression was decreased in thyroid carcinomas, but was normal in the other tissues. TSH-R expression was normal in most tissues studied and was decreased in only some thyroid carcinomas. In thyroid cancer tissues, a positive relationship was found between the individual levels of expression of NIS, TPO, Tg and TSH-R. No relationship was found with the age of the patient. Higher tumor stages (stages >I vs stage I) were associated with lower expression of NIS (P = 0.03) and TPO (P < 0.01). Expression of the Glut1 gene was increased in 1 of 24 adenomas and in 8 of 43 thyroid carcinomas. In 6 thyroid carcinoma patients, 131I uptake was studied in vivo; NIS expression was low in all samples; 3 patients with normal Glut-1 gene expression had 131I uptake in metastases, whereas the other 3 patients with increased Glut-1 gene expression had no detectable 131I uptake. In conclusion, this study shows 1) a reduced expression of NIS gene in most hypofunctioning benign and malignant thyroid tumors; 2) a differential regulation of the expression of thyroid-specific genes; 3) an increased expression of Glut-1 gene in some malignant tumors that may suggest a role for glucose derivative tracers to detect in vivo thyroid cancer metastases by positron emission tomography scanning.
在90个人类甲状腺组织中分析了4种甲状腺组织特异性基因[钠/碘同向转运体（NIS）、甲状腺过氧化物酶（TPO）、甲状腺球蛋白（Tg）、促甲状腺激素受体（TSH-R）]以及1型葡萄糖转运体（Glut1）基因的表达情况。从43例甲状腺癌（38例乳头状癌和5例滤泡状癌）、24例冷腺瘤、5例格雷夫斯甲状腺组织、8例毒性腺瘤和5例增生性甲状腺组织中提取信使核糖核酸；5例正常甲状腺组织用作对照。采用基于荧光TaqMan方法和荧光实时测量的动力学定量PCR方法。43例甲状腺癌中的40例（降低10至1200倍）和24例冷腺瘤中的20例（降低2至700倍）NIS表达降低；在毒性腺瘤和格雷夫斯甲状腺组织中NIS表达增加（高达140倍）。甲状腺癌中TPO表达降低，但冷腺瘤中TPO表达正常；在毒性腺瘤和格雷夫斯甲状腺组织中TPO表达增加。Tg表达在甲状腺癌中降低，但在其他组织中正常。TSH-R表达在大多数研究组织中正常，仅在一些甲状腺癌中降低。在甲状腺癌组织中，发现NIS、TPO、Tg和TSH-R的个体表达水平之间存在正相关。未发现与患者年龄有关。较高的肿瘤分期（II期及以上vs I期）与NIS（P = 0.03）和TPO（P < 0.01）表达降低相关。24例腺瘤中的1例和43例甲状腺癌中的8例Glut1基因表达增加。在6例甲状腺癌患者中，对131I摄取进行了体内研究；所有样本中NIS表达均较低；3例Glut-1基因表达正常的患者转移灶中有131I摄取，而其他3例Glut-1基因表达增加的患者未检测到131I摄取。总之，本研究表明：1）大多数功能减退的良性和恶性甲状腺肿瘤中NIS基因表达降低；2）甲状腺特异性基因表达存在差异调节；3）一些恶性肿瘤中Glut-1基因表达增加，这可能提示葡萄糖衍生物示踪剂在通过正电子发射断层扫描检测体内甲状腺癌转移方面的作用。
