甲状腺癌PCDH8基因的转录调控及临床意义

目的研究甲状腺乳头状癌、甲状腺滤泡状腺瘤、结节性甲状腺肿和正常甲状腺组织中原钙黏蛋白8(PCDH8)基因转录调控表达水平,分析PCDH8基因表达与甲状腺乳头状癌患者临床病理特征的关联性。方法选择该院2013～2015年的甲状腺组织标本118例,根据病理结果分为甲状腺乳头状癌组36例、甲状腺滤泡状腺瘤组30例、结节性甲状腺肿组31例和正常甲状腺组织组21例。采用荧光定量PCR法检测各组标本PCDH8基因的表达情况,分析PCDH8基因的表达情况与甲状腺乳头状癌患者临床病理特征的关联性。结果荧光定量PCR的结果显示,正常甲状腺组织组的PCDH8阴性表达率为28. 57%,低于甲状腺乳头状癌组(63. 89%)和甲状腺滤泡状腺瘤组(60. 00%),差异有统计学意义(P 0. 05);但与结节性甲状腺肿组(54. 84%)比较差异无统计学意义(P 0. 05)。PCDH8基因mRNA转录表达情况与肿瘤大小有显著关联(P 0. 05)。结论甲状腺乳头状癌中PCDH8基因表达下调,并与肿瘤大小存在关联,在甲状腺乳头状癌的诊断与治疗中有可能成为一种有潜在价值的生物学肿瘤标志物。     

甲亢与甲状腺癌

关于甲状腺功能亢进(甲亢)与甲状腺癌的关系历来存在着争论。本文旨在观察甲状腺癌与甲亢并存的频率。病人和方法资料来源于1970年～1985年期间治疗的甲状腺癌251例,其中乳头状癌160例,滤泡癌76例,其它癌15例。甲亢类型有弥漫性甲状腺肿、结节性甲状腺肿和自主性腺瘤。甲状腺癌手术时病人甲状腺功能正常,但     

Smad4蛋白表达在结节性甲状腺肿与甲状腺癌并存组织中的变化

目的探讨Smad4蛋白表达在结节性甲状腺肿与甲状腺癌并存组织中的变化。方法随机选取本院附属医院病理科收集的40例外科切除手术结节性甲状腺肿与甲状腺癌并存组织标本,作为研究组;另选取40例结节性甲状腺肿与甲状腺瘤并存组织标本作为对照1组,另选取40例结节性甲状腺肿组织标本作为对照2组,对三组患者标本中Smad4蛋白的表达及研究组各组织学分类患者标本中Smad4蛋白的表达进行统计分析。结果研究组患者标本中Smad4蛋白表达阳性率显著低于对照1组、对照2组(P0.05),而对照1组患者标本中Smad4蛋白表达阳性率又显著低于对照2组(P0.05);乳头状癌和滤泡状癌患者标本中Smad4蛋白表达阳性率均显著高于未分化癌患者(P0.05)。结论结节性甲状腺肿与甲状腺癌并存组织中Smad4蛋白表达能够帮助临床有效阐述患者病变的生物学行为并评估其预后。     

Galectin-3蛋白在甲状腺肿瘤中的表达及其意义

用免疫组化ABC法检测甲状腺良恶性肿瘤组织中Galectin3蛋白的表达,发现甲状腺癌组织的表达率明显高于癌旁组织、结节性甲状腺肿和甲状腺腺瘤组织的表达率,提示Galectin3蛋白是甲状腺癌,尤其是滤泡上皮起源的甲状腺癌的良好的肿瘤指标,有一定的临床应用价值。     

VEGF-C及TNF-α在乳头状与滤泡状甲状腺癌中的表达及其意义

目的 探讨血管内皮生长因子(VEGF)-C和肿瘤坏死因子(TNF)-α在甲状腺乳头状癌(PTC)和甲状腺滤泡状癌(FTC)中的表达及意义.方法 采用免疫组化SP法检测甲状腺乳头状癌45例(其中31例伴颈淋巴结转移)、甲状腺滤泡状癌17例(其中3例伴颈淋巴结转移)及18例正常甲状腺组织标本中VEGF-C及TNF-α表达情况.结果 在甲状腺癌中VEGF-C及TNF-α均有不同程度的表达,在乳头状癌中表达程度高于滤泡状癌,有淋巴结转移的肿瘤较无转移的肿瘤表达升高(均P＜0.05).结论 VEGF-C和TNF-α在PTC 中的表达高于FTC,提示VEGF-C和TNF-α可促进PTC与FTC发生淋巴转移.     

Galectin-3在甲状腺结节中的表达

目的研究galectin-3在甲状腺结节中的表达.方法应用免疫组化及RT-PCR方法检测甲状腺标本中galectin-3表达.结果无论采用免疫组化或RT-PCR方法,甲状腺癌组织的galectin-3表达率均较高（阳性率为89.7%和91.7%）,不同类型的癌组织中有较大差异,其中乳头状癌和滤泡状腺癌具有较高水平的表达（阳性率100%）.有淋巴结转移者galectin-3表达水平高于无淋巴结转移者.在良性甲状腺结节及正常甲状腺组织,采用免疫组化方法检测的25份甲状腺腺瘤标本和13份结节性甲状腺肿标本仅3例呈阳性,余均为阴性,10份正常甲状腺组织及25份癌旁组织均未发现galectin-3表达.结论galectin-3可作为鉴别良、恶甲状腺疾病的一个较有价值的肿瘤指标.     

MMP-2和HBME-1在分化型甲状腺癌中的表达及其临床意义

目的探讨基质金属蛋白酶(MMP)-2及间皮瘤相关抗体-1(HBME-1)在甲状腺肿瘤中的表达及其与甲状腺癌临床病理特征的相关性。方法通过免疫组化的方法检测MMP-2EY HBME-1左50例甲状腺癌(35例乳头状癌,15例滤泡状癌),15例腺瘤,15例多发结节,25例相临组织中的表达,通过甲醛固定及石蜡包埋。敏感性、特异性及精确性可以通过公式计算。结果 MMP-2及HBME-1在癌组织中的表达明显高于甲状腺良性肿瘤及正常组织(64%、98%)(P<0.05),特别是HBME-1。但是HBME-1在乳头状癌及滤泡状癌中的阳性率都很高,无统计学差异(P>0.05);相反,MMP-2在乳头状癌及滤泡状癌中表达具有统计学差异(P<0.05),在乳头状癌中有高表达(82.9%)。MMP-2在乳头状癌中的表达因肿瘤大小、分期、淋巴结转移情况而不同(P<0.05)。结论 MMP-2和HBME-1可成为分化型甲状腺癌的辅助诊断指标,特别是HBME-1。联合检测MMP-2和HBME-1有助于甲状腺乳头状癌及滤泡状癌的鉴别诊断。MMP-2可以作为乳头状癌发生和转移的预后因子。     

S期激酶相关蛋白2及细胞周期抑制蛋白p27在老年甲状腺癌患者癌组织中的表达及临床意义

目的研究S期激酶相关蛋白(Skp)2和细胞周期抑制蛋白p27在甲状腺癌癌组织中的表达及临床意义。方法首次就诊的老年甲状腺癌患者85例、甲状腺腺瘤老年患者40例和结节性甲状腺肿老年患者40例,采用免疫组织化学法检测甲状腺癌、甲状腺腺瘤和甲状腺肿组织中Skp2和p27蛋白的表达情况。结果 (1)甲状腺癌组织Skp2蛋白阳性表达率显著高于甲状腺腺瘤组织和甲状腺肿组织(P<0.001),甲状腺腺瘤组织和甲状腺肿组织Skp2蛋白阳性表达率差异无统计学意义(P>0.05);(2)甲状腺癌组织p27蛋白阳性表达率显著低于甲状腺腺瘤组织和甲状腺肿组织(P<0.001),甲状腺腺瘤组织和甲状腺肿组织p27蛋白阳性表达率差异无统计学意义(P>0.05);(3)Skp2蛋白的表达与肿瘤分期、周围组织侵犯情况及淋巴结转移有关(P<0.05或P<0.01),而与性别和肿瘤大小无关(P>0.05);(4)p27蛋白的表达与肿瘤分期、周围组织侵犯情况及淋巴结转移有关(P<0.05或P<0.01),而与性别和肿瘤大小无关(P>0.05);(5)甲状腺癌组织中Skp2与p27蛋白表达评分呈负相关(r=-0.657,P=0.016)。结论 Skp2和p27蛋白分别在甲状腺癌组织的表达呈负相关,两者参与了甲状腺癌的发生和发展。     

Bmi-1 mRNA在甲状腺乳头状癌中的表达及其生物学意义

目的观察Bmi-1 mRNA在甲状腺乳头状癌中的表达情况以及与甲状腺乳头状癌临床病理参数的关系。方法收集51例行甲状腺乳头状癌手术切除标本和同期住院的22例结节性甲状腺肿及瘤旁正常组织,用RT-PCR方法测定Bmi-1基因表达,并分析甲状腺乳头状癌临床病理参数与基因表达的关系。结果 Bmi-1 mRNA甲状腺乳头状癌组织中的表达高于良性结节性甲状腺肿及正常组织（P〈0.05）。Bmi-1 mRNA的高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 Bmi-1 mRNA高表达可能参与调控甲状腺乳头状癌的发生、发展过程,并进而影响其生物学特点及预后。     

c-Met在甲状腺乳头状癌患者肿瘤组织中的表达及其临床意义

目的探讨c-Met在甲状腺乳头状癌患者肿瘤组织中的表达及其临床意义。方法选取2010年6月-2016年6月住院治疗的甲状腺乳头状癌、甲状腺肿、甲状腺腺瘤女性患者各50例,分析全部患者临床、病理及随访资料,将甲状腺乳头状癌患者作为观察组,甲状腺腺瘤及结节性甲状腺肿患者作为对照A组与对照B组,分别观察并记录c-Met在甲状腺乳头状癌患者肿瘤组织中的表达情况,c-Met在结节性甲状腺肿、甲状腺腺瘤患者病理组织中的表达情况。结果在对各组进行年龄、基因突变、基因扩增、自分泌/旁分泌信号和c-Met活化、蛋白的超表达分析发现,观察组在基因突变、自分泌/旁分泌信号和c-Met活化、蛋白的超表达中表达水平明显高于对照组,(P0.05);在基因扩增方面,观察组与对照组有明显差异,在基因扩增方面观察组表达水平偏低(P0.05)。结论 c-Met在甲状腺乳头状癌患者肿瘤组织中的表达出现变异,cMet在甲状腺乳头状癌的治疗方面具有临床意义。     

Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues.

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.     

甲状腺疾病时甲状腺组织性激素受体的免疫组织化学研究

目的了解性激素及其受体在甲状腺疾病发病中的作用。方法用免疫组化ＡＢＣ法研究了不同甲状腺疾病时甲状腺组织中的性激素受体（ＡＲ、ＥＲ和ＰＲ）。结果在正常甲状腺组织中有少量的性激素受体表达,但阳性率不高;甲状腺癌组织中性激素受体的表达明显增加,尤其在乳头状腺癌组织中ＡＲ、ＰＲ增加更明显,不仅高于正常人也高于腺瘤和结节性甲状腺肿（Ｐ＜０．０１,０．０１,０．０５）;腺瘤和结节性甲状腺肿的ＥＲ明显高于正常人（Ｐ＜０．０１）;桥本甲状腺炎三种性激素受体的阳性率也高于正常人,但无统计学差异。结论虽然各种甲状腺疾病均多发于女性,但它们与性激素受体的关系不一样,甲状腺癌可能与雄激素及孕激素的作用增强有关,而良性甲状腺疾病与雌激素作用关系更密切     

结节性甲状腺肿伴良恶性乳头状增生的临床病理分析

收集结节性甲状腺肿（简称结甲）伴良恶性乳头状增生病变８１例，其中结甲伴良性乳头状增生５２例，结甲伴恶性乳头状增生（结甲伴乳头状癌）２１例，甲状腺乳头状腺瘤（实属结甲囊性变伴乳头状增生）１８例。经常规ＨＥ染色，光镜检查，根据近期共认标准重新诊断，结果表明，良恶性乳头状增生病变乳头的结构和细胞核的形态存在明显差异。原诊断为甲状腺乳头状腺瘤８例，复查后均符合结甲囊性变伴乳头状增生。笔者认为甲状腺癌的发生     

胃癌患者检测表皮生长因子及受体的意义

目的:探讨表皮生长因子(EGF)及其受体(EGFR)的表达与胃癌发生及胃癌生物学行为的关系。方法:采用免疫组化S-P法对50例胃癌进行研究。结果:EGF和EGFR在早期胃癌中的阳性率均为20％(2/10),在进展期胃癌的阳性率分别为62.5％(25/40)和60％(24/40),进展期胃癌EGF和EGFR的阳性率均显著高于早期胃癌(P<0.05)。有转移组的EGF及EGFR阳性率高于无转移组(P<0.05)。EGF及EGFR的表达与胃癌的组织学类型有关。结论:EGF及EGFR阳性的肿瘤可能具有更强的浸润与转移能力,检测EGF和EGFR有助于判断胃癌预后。     

Expression of the Axl receptor tyrosine kinase in human thyroid carcinoma.

Protein tyrosine kinases (PTKs) play a crucial role in regulating thyroid cell growth and differentiation. The Axl protein is a member of a new family of receptor tyrosine kinases, of which the ligand, Gas6, a protein S-related molecule, recently was proved to be a mitogenic factor for human thyroid cells. To further investigate the involvement of Axl in human thyroid carcinoma, we examined tissues obtained from 81 patients with thyroid carcinomas, 18 with adenomas, and 13 with adenomatous goiters by immunohistochemistry and in situ hybridization. In addition, among the thyroid carcinomas, we compared Axl expression levels with the grade of differentiation and lymph node metastasis of the carcinoma. Axl was expressed faintly in adenomatous goiter and adenomas, but not in normal thyroid tissues. Among the 81 cases of thyroid carcinoma, 70 (86.4%) showed a positive staining for the Axl protein. Immunopositive (+ +) was detected in papillary carcinomas and anaplastic carcinomas. The level of Axl expression, however, had no correlation with the presence of lymph node metastasis in thyroid carcinomas. In situ hybridization also confirmed the presence of axl mRNA in thyroid carcinoma tissues. These findings suggest that Axl expression may be closely involved in human thyroid tumorigenesis.     

Telomerase activity in thyroid malignancy.

Telomerase activity seems to play a role in the development and pathogenesis of thyroid carcinoma. Its incidence of expression and its application as a tumor marker remain to be elucidated. Thyroid tissues obtained during thyroidectomy from 1996-1998 were rapidly frozen and stored at -80 degrees C until processed. Telomerase activity was determined using telomeric repeat amplification protocol (TRAP). Histology of the tissue examined (67 benign and 59 malignant) was reviewed. Telomerase activity was detected in 15 of 52 papillary carcinomas (29%); 1 of 1 thyroid lymphoma (100%); 1 of 2 anaplastic carcinomas (50%); and 2 of 16 lymphocytic thyroiditis specimens (13%). Telomerase activity was not detectable in 35 normal thyroid, 9 follicular adenoma, 7 nodular hyperplasia, 2 follicular carcinoma, and 2 medullary carcinoma. Lymphocytic thyroiditis was detected in 8 of 37 (22%) apparently normal thyroid tissues adjacent to papillary thyroid carcinoma and telomerase activity was present in 2 of these 8 specimens (25%). In conclusion, telomerase does not appear to be frequently activated in papillary thyroid carcinoma. The association of lymphocytic thyroiditis with papillary thyroid carcinoma may limit its clinical usefulness as a tumor marker.     

Evaluation of insulin-like growth factor II, cyclooxygenase-2, ets-1 and thyroid-specific thyroglobulin mRNA expression in benign and malignant thyroid tumours

OBJECTIVE: We evaluated three markers (insulin-like growth factor II (IGF-II), cyclooxygenase-2 (COX-2) and ets-1) of thyroid growth stimulation and cell transformation together with a thyroid-specific marker (thyroglobulin (Tg)) for their potential to differentiate benign and malignant follicular thyroid neoplasia (FN). DESIGN AND METHODS: mRNA expression levels were determined by real-time PCR in 100 snap-frozen thyroid samples: 36 benign thyroid nodules with different histology and function (19 cold (CTN) and 17 toxic thyroid nodules (TTN)), 36 corresponding normal thyroid tissues of the same patients, eight Graves' disease (GD) thyroids, 10 follicular thyroid carcinomas (FTC) and 10 papillary thyroid carcinomas (PTC). RESULTS: Mean IGF-II and COX-2 levels were not significantly altered between benign and malignant thyroid nodules (IGF-II) or nodular (FTC, TTN, CTN) and normal thyroid tissues (COX-2). In contrast, eight- to tenfold upregulation of ets-1 was observed in PTC and three- to fourfold upregulation of ets-1 was observed in FTC (and GD) compared with benign thyroid nodules and normal thyroid tissues. In addition, thyroglobulin mRNA expression was markedly downregulated (50- to 100-fold) in FTC, PTC and GD samples compared with benign nodular and normal thyroid tissues. Hence an ets-1/Tg ratio >20 distinguished differentiated thyroid cancer from benign nodular or normal thyroid tissue. We then studied ets1- and Tg mRNA expression levels in fine needle aspiration cytology (FNAC) samples. However, in a consecutive series of 40 FNAC samples only equivocal results were obtained on 38 benign and two malignant (FTC) thyroid tumour samples. CONCLUSIONS: Upregulation of ets-1 and downregulation of Tg mRNA expression occur in differentiated thyroid cancer and may facilitate pre-operative identification of thyroid malignancy depending on further evaluation of these potentially promising markers in a larger series of benign and malignant thyroid tumours and their FNAC samples.     

Laminin receptors in differentiated thyroid tumors: restricted expression of the 67-kilodalton laminin receptor in follicular carcinoma cells.

The expression of integrin laminin receptors was investigated in normal thyroid primary cultures; immortalized normal thyroid cells (TAD-2); papillary (NPA), follicular (WRO), and anaplastic (ARO) thyroid tumor cell lines; seven thyroid tumors (four papillary and three follicular carcinomas); and normal thyroid glands. The expression of alpha1beta1, alpha2beta1, alpha3beta1, alpha6beta1, and alpha6beta4 was found in all tumor specimens and in tumor cell lines, whereas normal thyroid cells and TAD-2 cells lacked the expression of alpha6beta4. Despite the presence of several integrin laminin receptors, adhesion of TAD-2, NPA, and ARO cells to immobilized laminin-1 was poor, whereas WRO cells and follicular carcinoma-derived cells displayed a strong adhesion. Indeed, WRO and follicular carcinoma-derived cells showed expression of a nonintegrin laminin receptor, the 67-kDa high affinity laminin receptor (67LR). TAD-2, NPA, and ARO cells as well as nodular goiter, toxic adenoma, follicular adenoma, and papillary carcinoma-derived cells did not express the 67LR. Adhesion of WRO and follicular carcinoma-derived cells to laminin-1 was specifically inhibited by a recombinant polypeptide containing laminin-binding domains of 67LR, demonstrating that this receptor confers to follicular carcinoma cells attachment capacity to laminin. Moreover, tissue specimens from follicular carcinomas expressed the 67LR, whereas follicular adenomas and normal thyroid tissues were negative. In thyroid tumors, integrin receptors, although abundant, participate weakly in adhesion to laminin. The expression in follicular carcinoma cells of a functional, high affinity 67LR together with nonfunctional integrin LM receptors could be responsible for the tendency of follicular carcinoma cells to metastasize by mediating stable contacts with basal membranes.     

食管支架术后再狭窄组织中表皮生长因子及其受体的表达分析

目的 研究动物食管支架置入术后不同时间食管组织中表皮生长因子(EGF)、表皮生长因子受体(EGFR)的表达状况，以及与再狭窄形成的关系。方法 将16只食管支架术后再狭窄模型犬分为4组，分别于术后1、2、4、8周取材，另设立6只对照犬，所有样本采用免疫组织化学(SABC)及RT—PCR方法检测支架术后组织中EGF、EGFR的蛋白及mRNA表达。结果 支架术后1、2周食管组织中，EGF、EGFR的mRNA和蛋白均有明显表达，表达量较正常组织显著增强，几乎所有组织均不同程度的表达EGF、EGFR。4周时表达显著减弱，术后8周其表达基本消失。EGF的阳性细胞主要是巨噬细胞及部分血管内皮细胞与平滑肌细胞；EGFR的着色细胞主要是巨噬细胞、淋巴细胞及成纤维细胞。结论 食管支架术后，局部组织中淋巴细胞、巨噬细胞以及成纤维细胞增殖活性的变化与再狭窄的病理过程存在密切的关系，是重要的调节细胞。