NIS蛋白表达对甲状腺癌诊断及131I疗效预测的相关性研究

目的探讨钠碘同向转运体(Na /I-symporter,NIS)蛋白表达在甲状腺癌诊断及术后131Ⅰ治疗效果预测方面的临床应用价值。方法选取我院1998~2006年病理诊断为甲状腺癌的31例患者,采用免疫组化法检测NIS蛋白在细胞中的表达部位、阳性细胞数及表达强度,并以免疫组化评分(immunohistochemical scores,I HS)表示,研究在不同病理类型甲状腺癌原发灶及转移灶中NIS蛋白的表达情况。结果阳性对照Grave病甲状腺组织中NIS蛋白呈强表达,定位于甲状腺滤泡上皮细胞基底部质膜或周边质膜;阴性对照不表达。31例甲状腺癌原发灶细胞胞浆均为NIS阳性表达,其中80.65%的患者IHS≥4分;30例转移灶中,除2例不表达外,其余为胞浆阳性。转移灶与原发灶中NIS蛋白表达具有正相关;甲状腺癌原发灶NIS蛋白表达与甲状腺癌病理类型有关,在乳头状癌(PTC)中最强,滤泡状腺癌(FTC)中次之,滤泡型乳头状癌(fvPTC)中表达较弱。结论NIS蛋白表达在甲状腺癌中主要定位于胞浆,其摄碘障碍可能主要是错误定位的结果。NIS蛋白在不同甲状腺疾病组织中的表达差异有助于甲状腺良、恶性疾病,尤其是FTC与滤泡型腺瘤的鉴别诊断,也有助于不同病理类型甲状腺癌的鉴别。原发灶NIS蛋白表达水平对预测转移灶131I疗效有帮助,NIS蛋白的免疫组化检测有广阔的临床应用前景。     

钠碘转运体与分化型甲状腺癌

钠碘转运体(NIS)是甲状腺滤泡细胞基底膜上的一种糖蛋白，具有选择性和主动性转运碘(I^-)到甲状腺滤泡细胞内的功能。NIS不仅存在于甲状腺，也存在于腮腺、胃黏膜、乳腺等多种组织。有报道，将NIS基因转染到NIS低表达的甲状腺癌细胞和其他类型的肿瘤细胞内，肿瘤细胞表达NIS，增加了^131I的摄取。在分化型甲状腺癌(DTC)和其他肿瘤，^131I治疗展现了良好的前景。     

不同碘摄入量对大鼠促甲状腺激素受体mRNA与钠碘转运体蛋白表达的影响

目的:观察不同碘摄入量对大鼠甲状腺组织中促甲状腺激素受体(TSHR)mRNA和钠碘转运体(NIS)蛋白表达的影响。方法:36只SD大鼠随机均分为低碘组、适碘组和高碘组。于实验第4,8周后分批处死大鼠,分别用实时荧光定量PCR和免疫组织化学法检测甲状腺组织中TSHR mRNA和NIS蛋白表达水平。结果:实验4周后,与适碘组比较,TSHR mRNA表达量在低碘组明显升高(P<0.05),而在高碘组略有降低,差异无统计学意义(P>0.05);NIS蛋白表达率在低碘组有所升高,高碘组有所降低,但差异均无统计学意义(均P>0.05)。实验8周后,与适碘组比较,低碘组和高碘组的TSHR mRNA和NIS蛋白表达水平均明显低于适碘组(均P<0.05),其中NIS蛋白表达率分别为同组4周后的44.03%和56.12%(均P<0.05)。结论:无论碘过量或碘缺乏,长期碘营养障碍均可降低NIS的表达,且该影响可能是通过TSH-TSHR信号通路活性改变所介导。     

钠/碘转运体在甲状腺乳头状癌中的表达（附43例报道）

目的：探讨钠/碘转运体在甲状腺乳头状癌组织中的表达。方法：采用免疫组化的方法,检测有随访资料的43例甲状腺乳头状癌石蜡组织中钠,碘转运体的表达。结果：43例中钠/碘转运体阴性表达32例（74％）．阳性表达11例（26％）,钠,碘转运体的表达与甲状腺乳头状癌的淋巴结转移有明显相关性（p〈0．05）。结论：钠/碘转运体在甲状腺乳头状癌中主要为表达降低或定位于细胞浆表达,可能是导致其摄碘率降低的主要因素,钠／碘转运体阴性表达的甲状腺乳头状癌可能表现的更具淋巴结转移的倾向.     

钠碘转运体和甲状腺过氧化物酶mRNA在甲状腺病变中的表达及意义

目的 探讨甲状腺滤泡源性肿瘤及病变中钠碘转运体（NIS）和甲状腺过氧化物酶（TPO）mRNA的表达及意义。方法 应用逆转录-聚合酶链反应（RT-PCR）技术，对55例甲状腺肿块的NIS mRNA和TPO mRNA丰度进行了检查。结果NIS mRNA在5种不同病理类型以及4种不同状态间的表达差异无统计学意义（P〉0．05）。而TPO mRNA的比较，差异均有统计学意义（P〈0．05），良性病变组TPO mRNA表达率明显高于恶性病变组而接近于正常对照组。表达TPO mRNA病例的半定量观察结果，良、恶性病变组间TPO mRNA的光密度积分值（mRNA丰度）差异具有统计学意义（P〈0．01），良性病变组明显高于恶性病变组。结论良恶性甲状腺滤泡源性肿瘤及病变中均存在着NIS的缺陷；TPO作为甲状腺良性肿瘤和病变的标志物有一定的应用价值；临床甲状腺结节性病变如同位素扫描为冷结节，细针穿刺活检（FNAB）检查TPO阴性者应视为手术适应证。     

人甲状腺组织中钠碘转运体基因表达的研究

钠碘转运体(The sodium-iodide symporter-NIS)定位于甲状腺滤泡细胞的基底外侧膜,将2个钠离子和1个碘离子同时转运人甲状腺细胞,从而形成甲状腺细胞内碘的浓聚.我们采用实时荧光定量逆转录一聚合酶链反应(Real timeQuantitative PCR)方法测定人甲状腺乳头状癌及转移淋巴结组织中NIS mRNA的表达,探讨hNIS mRN-A和甲状腺乳头状癌及转移淋巴结的关系.     

甲状腺癌中E-cadherin的表达及临床意义

目的 研究E-cadherin在甲状腺癌中的表达及其临床意义。方法 应用免疫组化方法，对19例甲状腺乳头状腺癌，12例甲状腺滤泡伏腺癌和17例甲状腺髓样癌进行了E-cadherin表达的检测。结果 8例（42．1％）甲状腺乳头腺E-cadherin表达阳性，5例（41．7％）甲状腺滤泡状腺癌E-cadherin表达阳性，11例（64．7％）甲关状腺样癌E-cadherin表达阳性。E-cadherin表达在甲状腺癌各病理类型与甲状腺腺瘤之间比较，其阳性率差异有显著性；但在甲癌的三种病理类型之间其阳性率差异无显著性。E-cadherin在甲状腺癌中的表达与年龄有相关性，但与其它各临床病理参数无明显的相关性。结论 在甲状腺上皮细胞表面的E-cadherin具有一定的破坏或功能不正常，但尚不能成为甲状腺癌独立的预后指标。     

Galectin-3在甲状腺癌中的表达及其临床意义

目的：探讨 Galectin-3在甲状腺肿瘤组织中的表达及其临床意义。方法：运用免疫组织化学方法，检测50 例甲状腺癌(其中甲状腺乳头状癌32例，甲状腺滤泡状癌18例)、45例甲状腺腺瘤及20例正常甲状腺组织中 Galectin-3的表达。结果：50例甲状腺癌中，Galectin-3表达阳性者达45例(90． 0%)，其中29例为强阳性；45例甲状腺 腺瘤中，仅2例(4． 4%)Galectin-3阳性者，且均为弱阳性；20例正常甲状腺 Galectin-3均为阴性。Galectin-3表达阳性 率在甲状腺癌中显著高于甲状腺腺瘤及正常甲状腺(P＜0． 01) 。甲状腺乳头状癌与滤泡状癌 Galectin-3表达阳性率无 显著差异(P＞0． 05) 。淋巴结转移者 Galectin-3表达阳性率与无淋巴结转移者相比无显著差异(P＞0． 05) ，但淋巴结转移 者 Galectin-3阳性表达强度显著高于无淋巴结转移者(P＜0． 05) 。结论：Galectin-3可作为鉴别甲状腺良、恶性肿瘤的重 要参考指标，其表达强度的检测有助于甲状腺癌转移的预测。     

甲状腺乳头状癌BRAFV600E突变和钠/碘转运体表达的研究

目的 研究甲状腺乳头状癌(PTC)中BRAFV600E突变及钠/碘转运体(NIS)的表达,并分析其临床意义.方法 对40例PTC标本行BRAFV600E直接测序,检测其突变率;运用免疫组化检测NIS的表达情况.分析BRAFV600E突变与PTC临床病理特征的相关性及NIS的表达与BRAFV600E突变的相关性.结果 BRAFV600E突变率为57.5％;NIS阳性表达率为12.5％.BRAFV600E突变与甲状腺包膜侵犯及肿瘤的复发明显相关(P＜0.05).在BRAFV600E突变的PTC中只有1例NIS阳性表达(4.3％),NIS阳性表达在BRAFV600E突变的PTC中显著降低(P=0.011). 结论 BRAFV600E突变的PTC更具侵袭性、复发率较高及预后差;NIS阳性表达降低,可能是PTC摄碘降低的主要原因.     

PTEN基因在甲状腺癌组织中的表达及其意义

摘要：为探讨PTEN基因在甲状腺癌中的表达及其与甲状腺癌生物学行为的关系，笔者采用免疫组化方法检测PTEN基因在不同甲状腺组织中的表达。结果示，甲状腺癌组织PTEN基因的阳性表达率明显低于甲状腺正常组织和甲状腺腺瘤组织；PTEN基因表达与甲状腺癌的TNM分期、淋巴结转移呈负相关。提示PTEN基因表达的降低在甲状腺癌的发生和转移过程中起重要作用。     

CD10在甲状腺疾病中的表达及意义

目的研究CD10在甲状腺疾病中的表达及意义。方法收集70例甲状腺良、恶性病变组织，其中15例滤泡性腺瘤、15例腺瘤性甲状腺肿、30例乳头状癌和10例滤泡性癌。采用免疫组织化学的方法检测CD10在上述病变中的表达。结果9例滤泡型乳头状癌中，7例表达CD10，CD10阳性率为77％。10例滤泡性癌中，8例表达CD10，阳性率为80％。而在滤泡性腺瘤和腺瘤性甲状腺肿及21例普通型乳头状癌组织中CD10均不表达。CD10在滤泡型乳头状癌和滤泡性癌中的阳性率显著高于滤泡性腺瘤和腺瘤性甲状腺肿中的阳性率（P〈0．01）。结论对CD10表达的检测有助于对甲状腺滤泡性癌和滤泡型乳头状癌的诊断。     

Profound hypokalemia and hypochloremic metabolic alkalosis during thiazide therapy in a child with Pendred syndrome

Pendred syndrome is a recessive autosomal disorder characterized by thyroid goiter and sensorineural hearing loss. The Pendred syndrome gene (SLC26A4) encodes a new anion exchanger named pendrin which mediates iodide transport by thyrocytes and regulates ion and fluid transport by the endolymphatic sac epithelium. Pendrin defects result in inner ear malformations, with enlargement of the endolymphatic sac and duct in association with a large vestibular aqueduct. Furthermore, patients may develop endolymphatic hydrops requiring diuretic therapy, mainly in the form of thiazides. Pendrin could also account for apical Cl(-)/ HCO3(-) exchange at level of intercalated cells of the cortical collecting duct in the kidneys, however, humans with Pendred syndrome have no symptoms attributable to renal pendrin abnormalities in basal conditions. We report the case of a child with Pendred syndrome and intercurrent endolymphatic hydrops, who developed profound hypokalemia and severe hypochloremic metabolic alkalosis (potassium 1.7, chloride 70, sodium 129, HCO3 43.8, base excess +17.8 mmol/l, pH 7.52) following thiazide therapy. In subjects with Pendred syndrome thiazide therapy seems to provoke more severe Cl(-) and extracellular volume depletion. A possible explanation could be the defective action of the disrupted pendrin, which exacerbates the effects of the inhibition of C1(-) reabsorption mediated by the thiazide-sensitive NaCl cotransporter (SLC12A3).     

Distribution of Na<Superscript>+</Superscript>/I<Superscript>–</Superscript> Symporter in Thyroid Cancers in an Iodine-deficient Population: An Immunohistochemical Study

Background There are significant differences in the prevalence and behavior of differentiated thyroid cancers (DTC) in the iodine-deficient areas (IDA) and iodine-sufficient areas (ISA) of the world. The sodium iodide symporter (NIS), mediates active transport of iodide across the basolateral aspect of the thyroid follicular cell. However, no study had specifically addressed the issue of expression of sodium iodide symporter (NIS) in thyroid cancer specimens from IDA. The aim of the present study was to find an expression pattern of NIS in DTC in an iodine-deficient population, and to correlate it with histological subtypes, i.e., papillary carcinoma (PTC), follicular carcinoma (FTC), poorly differentiated carcinoma (PDTC), as well as with clinicopathological risk factors and iodine (¹³¹I) uptake by distant metastases. Methods Immunohistochemistry was carried out in 39 cases of thyroid cancer (41 samples) including PTC (15), FTC (10), PDTC (9), anaplastic cancer (5), and resected metastases (2). Expression was correlated with the patient’s age, sex, tumor size, presence or absence of extrathyroidal invasion, distant and lymph node metastases, and whole body radioiodine scan. Results Overall, 61.8% of DTC patients showed NIS expression. There was no significant difference in expression rate between PTC (73.3%) and FTC (70.0%). However, expression was significantly less in PDTC (33.3%). There was no correlation between NIS expression and any clinicopathological risk factor (p > .05). The results of NIS expression were not concordant with ¹³¹I uptake by metastases in 4 of 10 cases. ¹³¹I uptake was absent in one case despite the finding that a metastatic site itself showed NIS expression in that case, whereas in the remaining 9 cases ¹³¹I uptake was present although three cases did not show NIS expression. Conclusions In our experience, overall expression of NIS was comparable to other studies from ISA. We conclude that expression may not accurately predict radioactive iodine (RAI) uptake by metastases. This study was supported by an intramural grant provided by Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.     

Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status

BACKGROUND: Pendrin belongs to a superfamily of Cl-/anion exchangers and is expressed in the inner ear, the thyroid gland, and the kidney. In humans, mutations in pendrin cause Pendred syndrome characterized by sensorineural deafness and goiter. Recently pendrin has been localized to the apical side of non-type A intercalated cells of the cortical collecting duct, and reduced bicarbonate secretion was demonstrated in a pendrin knockout mouse model. To investigate a possible role of pendrin in modulating acid-base transport in the cortical collecting duct, we examined the regulation of expression of pendrin by acid-base status in mouse kidney. METHODS: Mice were treated orally either with an acid or bicarbonate load (0.28 mol/L NH4Cl or NaHCO3) or received a K+-deficient diet for one week. Immunohistochemistry and Western blotting was performed. RESULTS: Acid-loading caused a reduction in pendrin protein expression levels within one day and decreased expression to 23% of control levels after one week. Concomitantly, pendrin protein was shifted from the apical membrane to the cytosol, and the relative abundance of pendrin positive cells declined. Similarly, in chronic K+-depletion, known to elicit a metabolic alkalosis, pendrin protein levels decreased and pendrin expression was shifted to an intracellular pool with the relative number of pendrin positive cells reduced. In contrast, following oral bicarbonate loading pendrin was found exclusively in the apical membrane and the relative number of pendrin positive cells increased. CONCLUSIONS: These results are in agreement with a potential role of pendrin in bicarbonate secretion and regulation of acid-base transport in the cortical collecting duct.     

甲状腺乳头状癌中PDK1、ZEB1和Vimentin的表达及其临床意义

目的:探讨磷酸肌醇依赖性蛋白激酶1 (PDK1)、E盒结合锌指蛋白1(ZEB1)和波形蛋白(Vi-mentin)在甲状腺乳头状癌(PTC)组织中的表达情况,并探究三指标与PTC临床病理参数的相关性.方法:免疫组化EnVision法检测206例PTC及45例癌旁组织中PDK1、ZEB1和Vimentin表达,分析其与PT...     

Increased iodine uptake in thyroid carcinoma after treatment with sodium butyrate and decitabine (5-Aza-dC).

OBJECTIVE: To determine if epigenetic-modifying drugs can increase iodine uptake in thyroid carcinoma cell lines. STUDY DESIGN: Human thyroid carcinoma cell lines were tested for iodine uptake before and after treatment with epigenetic-modifying agents. RESULTS: Thyroid carcinoma cell lines DRO and 2-7 had high levels of DNA methylation (74% and 80%) compared with normal thyroid tissue (6%) (P < 0.05). This finding correlated with low levels of sodium iodide symporter (NIS) expression in the untreated thyroid carcinoma cell line. Combination treatment with the epigenetic-modifying agents 5-aza-2'-deoxycytidine and sodium butyrate resulted in increases in NIS messenger RNA levels, global histone acetylation, and 9- and 8-fold increases in I(125) uptake for the DRO and 2-7 cells, respectively. CONCLUSIONS: Epigenetic-modifier drugs represent a novel adjuvant treatment for those patients with radioablation-resistant thyroid cancer. SIGNIFICANCE: Epigenetic-modifying agents show potential for treatment of radioablation-resistant thyroid cancer.