真核细胞起始因子4E与C-myc在甲状腺乳头状癌中的表达

目的观察真核细胞起始因子4E(eukaryotic initiation factor4E,eIF4E)及C-myc在甲状腺乳头状癌中的表达,并探讨两者间的相关性及它们与甲状腺乳头状癌的侵袭、转移等临床病理特征间的关系。方法采用免疫组化EnVin-sion法检测66例甲状腺乳头状癌、20例结节性甲状腺肿伴乳头状增生及上述病例的病变周围正常甲状腺组织中eIF4E和C-myc的表达情况。结果在正常甲状腺、结节性甲状腺肿伴乳头状增生及甲状腺乳头状癌中,eIF4E的阳性率分别为11.6%(10/86)、50.0%(10/20)和84.8%(56/66)(P<0.01),C-myc的阳性率分别为21.0%(18/86)、50%(10/20)和78.8%(52/66)(P<0.01)。eIF4E仅与乳头状癌的腺外侵袭和淋巴结转移有关(均P<0.05),C-myc仅与乳头状癌的淋巴结转移有关(P<0.01)。eIF4E及C-myc在乳头状癌中的表达呈正相关(rs=0.327,P<0.05)。结论与癌旁正常组织和良性病变相比,eIF4E和C-myc在甲状腺乳头状癌中存在过表达。eIF4E的过表达与甲状腺乳头状癌的腺外侵袭和淋巴结转移有关,C-myc的过表达与甲状腺乳头状癌的淋巴结转移有关,提示二者在甲状腺乳头状癌的进展中可能发挥重要的作用。     

不同性质甲状腺结节与微血管密度关系的研究

目的:探讨不同性质甲状腺结节与微血管密度关系,提高认识.方法:分别选取甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织,病理切片行常规HE染色及免疫组化SP染色.在高倍视野(×400)下选取5个血管着色密集区进行计数并取其平均数,MVD值=(n1 +n2+n3+n4+n5)/5.结果:(1)甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织平均MVD值分别为(65.54±19.21)个/HP、(54.54±11.76)个/HP、(47.85± 10.92)个/HP、(21.82±7.43)个/HP,甲状腺乳头状癌MVD值显著高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织(P＜0.05).甲状腺腺瘤、结节性甲状腺肿MVD值显著高于正常甲状腺组织(P＜0.05).(2)伴有淋巴结转移的甲状腺乳头状癌患者MVD值显著高于不伴有淋巴结转移者(P＜0.05);男性甲状腺乳头状癌患者MVD值显著高于女性患者(P＜0.05);＞40岁及≤40岁甲状腺乳头状癌患者MVD值间无统计学差异(P＞0.05).结论:甲状腺乳头状癌MVD值显著高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织,且伴有淋巴结转移的甲状腺乳头状癌患者MVD值显著高于不伴有淋巴结转移者.     

抑癌基因PTEN 在甲状腺乳头状癌中的表达及临床意义*

目的:通过免疫组织化学方法检测PTEN基因在正常甲状腺组织、甲状腺良性肿瘤组织、甲状腺乳头状癌癌组织中的表达水平并进行比较,探讨其对甲状腺乳头状癌诊断和治疗的意义。方法:采用SP免疫组化方法,用已知阳性组织做阳性对照,以磷酸盐缓冲液(PBS)代替一抗做阴性对照,分别作HE染色和免疫组织化学染色。结果:PTEN蛋白在三组组织中的表达差异具有显著性(P<0.001);正常甲状腺组织、甲状腺良性肿瘤组织中的阳性率分别为100%和82.5%,均显著高于甲状腺癌组织中的45%(P<0.05),即PTEN在甲状腺癌中表达显著降低;PTEN在甲状腺乳头状癌淋巴结转移组和无淋巴结转移组阳性表达率分别为15%和60%,差异有显著性(x2=10.91,P=0.001);PTEN在甲状腺乳头状癌在包膜侵犯组和无侵犯组的阳性表达率分别为25.93%和60.61%,差异有显著性(x2=7.22,P=0.007);PTEN在甲状腺癌淋巴结转移组和包膜侵犯组的阳性表达强度显著低于无淋巴结转移和包膜侵犯组(P<0.01),有统计学意义。结论: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。     

HIF-1a、VEGF和CXCR4在甲状腺乳头状癌中的表达及意义

目的研究乏氧诱导因子1a(HIF-1a)、血管内皮生长因子(VEGF)和趋化因子受体4(CXCR4)在甲状腺乳头状癌组织中的表达及与临床病理因素的关系。方法应用免疫组化SP法检测120例甲状腺乳头状癌组织和60例正常对照组织中的HIF-1a、VEGF及CXCR4的表达情况,统计分析相关临床病理因素。结果 HIF-1a、VEGF及CXCR4在甲状腺乳头状癌中的阳性表达率分别为65.0%(78/120)、56.8%(68/120)、60.0%(72/120);三者的阳性表达与甲状腺乳头状癌的淋巴结转移及临床病理分期密切相关(P0.01);三者的表达之间存在一定的相关性(P0.05)。多因素分析发现,TNM分期,HIF-1a和CXCR4与甲状腺乳头状癌淋巴结转移密切相关(均P0.05)。结论 HIF-1a、VEGF及CXCR4与甲状腺乳头状癌的发生、发展相关,特别在甲状腺乳头状癌淋巴结转移中发挥重要作用,三者的检测在甲状腺乳头状癌的临床诊断及治疗中具有重要的指导意义。     

分子生物学法分析青少年甲状腺肿物临床病理及特点

探讨青少年甲状腺肿物的临床病理学特点,甲状腺癌的复发、转移和结节性甲状腺肿复发的可能相关因素。按WHO病理分型标准和国际抗癌联盟(UICC)TNM分期标准回顾性分析青少年甲状腺肿物124例及其中部分甲状腺癌和结节性甲状腺肿的随访资料。124例甲状腺肿物患者男女比例约为1 3,甲状腺癌39例(31.5%),其中乳头状癌35例,滤泡癌3例,髓样癌1例;甲状腺腺瘤59例(47.6%),结节性甲状腺肿11例(8.9%),结节性甲状腺肿伴腺瘤7例(5.6%),甲状腺炎5例(4%),甲状舌管囊肿3例(2.4%)。本组资料显示,青少年甲状腺癌以乳头状癌为主,其复发、转移与组织学亚型为弥漫硬化型及甲状腺包膜和其外软组织受侵状态相关。虽然常见淋巴结转移、肺转移以及局部侵犯周围软组织,但患者总体预后较好。结节性甲状腺肿的复发与病变弥漫位于双叶有关,而与患者性别、年龄和是否伴有乳头样及腺瘤样增生关系不密切。     

Wnt10a在甲乳癌及桥本合并甲乳癌中的差异表达（英文）

目的:探讨无翅型MMTV整合位点家族成员10a(Wnt10a)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和桥本合并甲状腺乳头癌(Hashimoto's thyroiditis associated with papillary thyroid carcinoma)中的表达及其临床意义。方法:采用q RT-PCR方法检测Wnt10a m RNA在41例新鲜甲状腺组织(PTC组织18例,HT合并PTC组织12例,结节性甲状腺肿组织11例)中的表达;用免疫组化SP法检测Wnt10a蛋白在50例甲状腺石蜡标本(PTC组织20例,HT合并PTC组织20例,结节性甲状腺肿组织10例)中的表达。结果:1 RT-PCR Wnt10a m RNA在甲状腺癌组织中的表达明显高于其在良性甲状腺肿瘤组织中的表达(P0.01),差异有显著性;Wnt10a m RNA在PTC、HT合并PTC组织中的阳性表达强度分别为2.49×10-5(0.68×10-5,15.28×10-5),1.26×10-5(0.97×10-5,13.73×10-5);P0.05,差异具有显著性。Wnt10a m RNA在PTC、HT合并PTC组织中的表达分别是结节性甲状腺肿组织的9.98、2.69倍。2SP法:Wnt10a在甲状腺癌组织中的表达明显高于其在良性甲状腺肿瘤组织中的表达。Wnt10a m RNA和蛋白在甲状腺癌组织中的表达与肿瘤大小、临床分期、淋巴结转移等临床因素无明显关系(P0.05),只与甲状腺癌组织的病理分型相关,(P0.05)。结论:Wnt10a在甲状腺乳头状癌和桥本合并甲状腺乳头癌中呈现高表达,且有差异性,有望作为甲状腺癌的病理分型的参考指标,有助于甲状腺癌的早期诊断及病理分型的判定,使患者得到及时有效治疗。     

表皮生长因子及受体在甲状腺肿瘤中的表达

目的:研究表皮生长因子(Epidermal Growth Factor,EGF)及受体(Epidermal Growth Factor Receptor,EGFR)及在甲状腺肿瘤中的表达。方法:应用免疫组织化学法检测91例甲状腺病变组织中EGFR和EGF的表达情况。结果:结节性甲状腺肿、甲状腺腺瘤、分化型甲状腺癌标本中EGFR表达的阳性率分别为15%、25%、68.62%,EGF表达的阳性率分别为10%、15%、68.62%,其中EGFR、EGF在分化型甲状腺癌与其余两组间差异均有统计学意义(P<0.05)。EGFR和EGF在甲状腺乳头状癌中的表达与性别、年龄、肿瘤大小、淋巴结转移、临床分期等临床因素无明显相关。结论:EGF和EGFR的表达可作为鉴别甲状腺肿瘤良恶性的一个指标。     

微小RNA-205 在甲状腺乳头状癌中的表达及临床意义

目的:观察微小RNA(microRNA,miRNA,miR)-205在甲状腺乳头状癌(PTC)中的表达并探讨其临床意义。方法:收集自2014年1月至2014年12月在我院甲状腺外科住院治疗的甲状腺乳头状癌患者的术后新鲜病理组织45例,其中男14例,女31例,年龄24-69岁,平均45.5岁。结节性甲状腺肿28例,癌旁正常甲状腺组织5例。提取各组织中的miRNA,应用实时荧光定量聚合酶链反应(RT-q PCR)方法检测miR-205的表达情况。结果:甲状腺乳头状癌miR-205的表达量较非肿瘤组织(结节性甲状腺肿、癌旁组织)明显下调[(1.06±1.76)vs(3.19±4.88),P=0.038]。伴淋巴结转移的PTC组织中miR-205表达量明显低于无淋巴结转移的PTC组织[(1.21±1.80)vs(9.59±1.60),P=0.003]。miR-205的相对表达与PTC患者性别、年龄及浸润与否均无显著相关性,而肿瘤直径呈显著相关性。结论:miR-205在PTC中的表达异常下调,可能与PTC的发生、侵袭和转移有关。     

Twist 在胸腺上皮性肿瘤中的表达及预后意义

目的:检测Twist在胸腺上皮性肿瘤的表达及其与预后的关系。方法:应用免疫组织化学pv6000法检测Twist在87例胸腺上皮性肿瘤(胸腺瘤71例,胸腺癌16例)中的表达情况,分析其与患者各项临床病理指标及预后的关系。结果:Twist蛋白在胸腺癌的阳性表达(81.3%)显著高于胸腺瘤组织(11.3%),其阳性表达的差异存在统计学意义(P<0.001),其在胸腺瘤各亚型之间表达的差异无统计学意义(P>0.05)。Twist阳性表达与胸腺上皮性肿瘤术后发生远处转移呈正相关关系(r=0.40,P=0.001)。Kaplan-Meier生存分析显示Twist阳性表达患者术后生存期低于Twist阴性表达患者(P<0.001)。结论:检测Twist蛋白表达情况对于鉴别胸腺瘤与胸腺癌可能有重要的参考价值,Twist阳性表达可能与术后发生远处转移有关并影响患者术后生存期。     

Wnt10a在甲乳癌及桥本合并甲乳癌中的差异表达

目的：探讨无翅型MMTV整合位点家族成员10a（Wnt10a）在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和桥本合并 甲状腺乳头癌（Hashimoto''s thyroiditis associated with papillary thyroid carcinoma）中的表达及其临床意义。方法：采用qRT-PCR方 法检测Wnt10a mRNA 在41 例新鲜甲状腺组织（PTC 组织18 例,HT 合并PTC 组织12 例,结节性甲状腺肿组织11 例）中的表 达;用免疫组化SP法检测Wnt10a 蛋白在50 例甲状腺石蜡标本（PTC 组织20 例,HT合并PTC组织20 例,结节性甲状腺肿组织 10 例）中的表达。结果：① RT-PCR Wnt10a mRNA 在甲状腺癌组织中的表达明显高于其在良性甲状腺肿瘤组织中的表达(P < 0.01) ,差异有显著性;Wnt10a mRNA在PTC、HT合并PTC组织中的阳性表达强度分别为2.49× 10-5（0.68× 10-5,15.28× 10-5）, 1.26× 10-（5 0.97× 10-5,13.73× 10-5）;P<0.05,差异具有显著性。Wnt10a mRNA 在PTC、HT 合并 PTC 组织中的表达分别是结节性甲 状腺肿组织的9.98、2.69 倍。②SP 法：Wnt10a 在甲状腺癌组织中的表达明显高于其在良性甲状腺肿瘤组织中的表达。Wnt10a mRNA 和蛋白在甲状腺癌组织中的表达与肿瘤大小、临床分期、淋巴结转移等临床因素无明显关系(P>0.05),只与甲状腺癌组织 的病理分型相关,（P<0.05)。结论：Wnt10a 在甲状腺乳头状癌和桥本合并甲状腺乳头癌中呈现高表达,且有差异性,有望作为甲状 腺癌的病理分型的参考指标,有助于甲状腺癌的早期诊断及病理分型的判定,使患者得到及时有效治疗。     

Survivin和CD44V6蛋白表达与甲状腺乳头状癌侵袭转移的关系

探讨甲状腺乳头状癌(papillary thyroid carcinoam,PTC)中生存素(survivin)和CD44v6蛋白表达及其意义.应用免疫组织化学方法检测66例PTC、20例甲状腺瘤(TA)、20例结节性甲状腺肿(NG)和15例正常甲状腺组织(NT)中survivin和CD44v6蛋白表达.结果表明,在PTC中,survivin和CD44v6表达阳性率分别为63.6%(42/66)和57.6%(38/66).PTC中survivin和CD44v6阳性表达率显著高于TA、NG和NT(P<0.05).survivin和CD44v6表达与PTC的侵袭转移呈显著正相关(P<0.05).survivin和CD44v6阳性表达与PTC侵袭、转移密切相关,检测survivin和CD44v6蛋白的表达可作为判断PTC生物学行为的参考指标.     

RET/PTC Rearrangements Are Associated with Elevated Postoperative TSH Levels and Multifocal Lesions in Papillary Thyroid Cancer without Concomitant Thyroid Benign Disease

RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto''s thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports. RET/PTC rearrangements were detected using TaqMan RT-PCR and validated by direct sequencing. No RET/PTC rearrangements were detected in benign thyroid tissues. RET/PTC rearrangements were detected in 23.68% (27/114) of PTC tissues. No association between thyroid function, clinicopathological parameters and lifestyle was observed either in total thyroid cancer patients or the subgroup of patients with concomitant disease. In the subgroup of PTC patients without concomitant disease, RET/PTC rearrangement was associated with multifocal cancer (P = 0.018). RET/PTC rearrangement was also correlated with higher TSH levels at one month post-surgery (P = 0.037). Based on likelihood-ratio regression analysis, the RET/PTC-positive PTC cases showed an increased risk of multifocal cancers in the thyroid gland (OR = 5.57, 95% CI, 1.39–22.33). Our findings suggest that concomitant diseases such as nodular goiter and Hashimoto''s thyroiditis in PTC may be a confounding factor when examining the effects of RET/PTC rearrangements. Excluding the potential effect of this confounding factor showed that RET/PTC may confer an increased risk for the development of multifocal cancers in the thyroid gland. Aberrantly increased post-operative levels of TSH were also associated with RET/PTC rearrangement. Together, our data provides useful information for the treatment of papillary thyroid cancer.     

Serum metabolic profiling and features of papillary thyroid carcinoma and nodular goiter

Thyroid carcinoma is a common endocrine malignancy worldwide, accounting for approximately 1% of all diagnosed cancers and about 91.5% of the malignancies of head and neck. However, differentiating malignant thyroid nodules from benign ones remains a diagnostic challenge. Thus, novel molecular markers that enable non-invasive diagnostics for malignant thyroid nodules are urgently needed. In the present study, a metabonomic investigation based on liquid chromatography-LTQ Orbitrap mass spectrometry was employed for serum metabolic profiling of 30 cases of papillary thyroid carcinomas (PTC), 80 cases of nodular goiters (benign thyroid nodules) and 30 cases of healthy controls. According to the results of multivariate statistical data analysis, the significantly changed metabolites among these three groups were defined. It was found that most of these metabolites decreased in the sera of both malignant and benign thyroid cases due to the increased metabolic rate, which is in accordance with clinical features. The major metabolic differences between benign and malignant nodules occurred in lipid metabolism. Especially, the content of 3-hydroxybutyric acid, an intermediate product of fatty acid metabolism, was much higher in the PTC group than that in the nodule goiter and control groups, indicating its potential as a diagnostic marker for PTC and nodular goiters. These results show that the serum metabolic profiling method is a powerful tool for distinguishing thyroid carcinoma from nodular goiter and healthy controls.     

Cell block alone as an ideal preparatory method for hemorrhagic thyroid nodule aspirates procured without onsite cytologists

OBJECTIVE: To study diagnostic efficacy of direct smears (DS) vs. cell block (CB) alone in hemorrhagic thyroid fine needle aspirations (FNAs) performed without a cytotechnologist or cytopathologist. STUDY DESIGN: Ultrasound-guided thyroid FNAs from an offsite location were retrospectively searched during a 53-month period. Aspirates in the initial 13 months were submitted as air-dried DSs. Subsequent specimens were submitted as CBs. Each case was classified into 1 of 4 categories: (1) nondiagnostic, (2) nonneoplastic, (3) follicular lesions and (4) papillary thyroid carcinoma (PTC). RESULTS: There were 77 aspirates: DS = 20 (26%) and CB = 57 (74%). Two cases had both DSs and CBs. Diagnoses of DS: nondiagnostic = 12 (60%); nonneoplastic = 7 (35%); follicular lesion = 1 (5%). Diagnoses of CB cases: nondiagnostic = 4 (7.0%); nonneoplastic = 43 (75.4%); follicular lesion, including 1 Hürthle cell neoplasm = 7 (12.3%), PTC = 3 (5.3%). Repeat FNAs on 4 nondiagnostic cases (3 DSs, 1 CB) utilizing the CB-only technique were diagnostic and included nodular goiter, follicular neoplasm, PTC, and reactive lymph node. CONCLUSION: Without onsite assessment, CB alone is superior to DSs for hemorrhagic thyroid FNAs. It shows increased diagnostic efficacy and slide reduction and obviates repeat FNAs.     

Multinucleated giant cells in fine needle aspirates. Can they help differentiate papillary thyroid cancer from benign nodular goiter?

OBJECTIVE: To determine whether multinucleated giant cells (MGCs) in fine needle aspirates can help differentiate papillary thyroid carcinoma (PTC) from benign nodular goiter (BNG). STUDY DESIGN: Specimens from 100 cases of PTC and 100 cases of BNG with surgical and pathologic proof were randomly retrieved. The morphologic characteristics and frequency distribution of the maximal size and number of MGC nuclei were analyzed. A retrospective review of medical records was also undertaken. RESULTS: MGCs were twice as frequent (40%) in PTC than in BNG (26%) (odds ratio = 1.90). Most MGCs in BNG tended to be smaller and ovoid, with foamy cytoplasm, and had fewer nuclei. No MGC in BNG was > 116 microns in diameter or had > 27 nuclei. In contrast, MGCs in PTC were more diverse in size, shape, cytoplasm and number of nuclei. No significant association was found between the presence or nature of MGCs and disease extent in PTC. CONCLUSION: The presence of large MGCs with dense cytoplasm in a thyroid nodule without clinical evidence of thyroiditis should prompt careful exclusion of associated PTC.     

乳头状甲状腺癌中线粒体DNA突变的研究

该文探究了线粒体DNA(mtDNA)突变与甲状腺癌的发生发展的相关性,评估了mtDNA拷贝数对甲状腺癌的诊断价值。根据对结节性甲状腺肿、滤泡状甲状腺腺瘤和乳头状甲状腺癌3组病人的mtDNA全基因测序和单倍型分型结果,统计3组病人mtDNA突变率及单倍型的差异,分析乳头状甲状腺癌病人的mtDNA突变率与临床资料的联系,最后通过荧光定量PCR检测3组病人的组织和血液样本中mtDNA的拷贝数。结果显示,乳头状甲状腺癌患者mtDNA的复合体I亚基编码区和tRNA编码区的突变率明显高于结节性甲状腺肿,在乳头状甲状腺癌患者中线粒体单体型M相对于单体型N有更低的淋巴结转移率,荧光定量PCR结果显示,甲状腺腺瘤和甲状腺癌组织中的mtDNA拷贝数明显高于结节性甲状腺肿,而在血液标本中,两者的mtDNA拷贝数均低于结节性甲状腺肿。这些结果表明,mtDNA拷贝数的变化和复合体I亚基编码区的突变可能作为甲状腺癌诊断的生物指标,而线粒体单体型N可能可以作为乳头状甲状腺癌恶性变化的预警指标。