Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours

Background:

Recent studies showed a significant upregulation of distinct microRNAs (miRNAs) in papillary thyroid carcinoma (PTC). The objective of this study was to explore whether this upregulation could also be assigned to distinct histomorphological variants of PTC, especially the follicular variant and other encapsulated follicular thyroid tumours.

Methods:

We used total RNA of 113 formalin-fixed paraffin-embedded tissues of 50 PTCs ((10 conventional type (PTC-CT), 10 tall cell variants (PTC-TCVs), 30 follicular variants (PTC-FVs)), 10 follicular adenomas (FAs), 10 multinodular goitres (MNGs), 21 follicular thyroid carcinomas and 22 well-differentiated tumours of unknown malignant potential (WDT-UMP) to analyse the miRNA expression pattern of five selected miRNAs (146b, 181b, 21, 221 and 222) using RT–PCR TaqMan miRNA assay to explore the diagnostic utility of this method.

Results:

The mean values of the expression pattern of all miRNAS in PTCs show a statistically significant difference from those in MNG and FA with fold changes up to 90 for miRNA 146b, P<0.001. No differences in expression pattern could be showed between MNG and FA. The PTC-FVs differ significantly from FA in all five miRNAS, from MNG in three and from WDT-UMP in one miRNA with fold changes between 1.7 and 21.2, but failed to be of diagnostic value regarding individual cases with substantial overlaps.

Conclusion:

We conclude that analysis of a set of five selected miRNAS distinguish common variants of PTC from FA/MNG but failed to be a useful diagnostic method in individual and doubtful cases, especially in the differential diagnosis of encapsulated follicular thyroid tumours.     

Expression of pendrin in benign and malignant human thyroid tissues

The Pendred syndrome gene (PDS) encodes a transmembrane protein, pendrin, which is expressed in follicular thyroid cells and participates in the apical iodide transport. Pendrin expression has been studied in various thyroid neoplasms by means of immunohistochemistry (IHC), Western blot and RT-quantitative real-time PCR. The expression was related to the functional activity of the thyroid tissue. Follicular cells of normal, nodular goitre and Graves' disease tissues express pendrin at the apical pole of the thyrocytes. In follicular adenomas, pendrin was detected in cell membranes and cytoplasm simultaneously in 10 out of 15 cases. Pendrin protein was detected in 73.3 and 76.7% of the follicular (FTC) and papillary (PTC) thyroid carcinomas, respectively, where pendrin was solely localised inside the cytoplasm. An extensive intracellular immunostaining of pendrin was observed in six out of 11 (54.5%) of positive FTCs and 19 out of 23 (82%) of PTCs. Focal reactivity was detected in one follicular- and three papillary carcinomas, whereas pendrin protein was absent in three of 15 FTC and four of 30 PTC; mRNA of pendrin was detected in 92.4% of thyroid tumours. The relative mRNA expression of pendrin was lower in cancers than in normal thyroid tissues (P<0.001). The pendrin protein level was found to parallel its mRNA expression, which was not, however, related to the tumour size and tumour stage. In conclusion, pendrin is expressed in the majority of differentiated thyroid tumours with high individual variability but its targeting to the apical cell membrane is affected.     

甲状腺滤泡性肿瘤形态定量分析

本文应用MIAS-300型图像分析系统对甲状腺良、恶性滤泡性肿瘤各30例及正常甲状腺组织8例进行了形态定量测定及比较分析,旨在探寻形态定量指标在鉴别诊断中的价值,并建立数据库,为计算机协助诊断疾病打下基础。常规制片,用个体测量法及群体测量法分别分析了每例100～145个滤泡上皮细胞,获得6项参数,包括核面积、核周长、核形状因子、等效核直径、核黑度及核质比。经统计学分析,显示上述各项参数在良恶之间比较均有高度显著性差异,表明这些参数在甲状腺滤泡性肿瘤良恶鉴别中有一定价值,为数学病理学研究提供了一定资料。     

甲状腺滤泡性肿瘤性质鉴别的分子标记物研究进展

在临床实践中,甲状腺滤泡癌和甲状腺滤泡性腺瘤的鉴别诊断一直是一个难点。由于组织病理学经常难以诊断,因此需要一些分子标记物来帮助确定甲状腺滤泡性肿瘤的良恶性。本文将目前已发现的几种最新的能辅助甲状腺滤泡性肿瘤良恶性鉴别诊断的分子标记物,予以综述介绍。     

Galectin-3 immunodetection in follicular thyroid neoplasms: a prospective study on fine-needle aspiration samples

Fine-needle aspiration cytology, which is well established to be accurate for the diagnosis of thyroid cancer, may be inconclusive for the follicular thyroid neoplasms. As galectin-3 was suggested to be a marker of malignant thyrocytes, we investigated whether this protein might be helpful in the diagnosis of aspirates classified as undeterminate by cytology. After establishing an easy processing of aspirates for galectin-3 immunodetection, a series of aspirates categorised as benign (n=63), malignant (n=17) or undeterminate (n=34) was prospectively analysed for galectin-3. Only the patients with malignant or undeterminate lesions underwent surgery. Most lesions (86%) diagnosed as malignant by cytology or after surgery were positive for galectin-3. The majority of lesions (94%) classified as benign by cytology or after surgery was negative for galectin-3. The positive and negative predictive values were 83 and 95%, respectively. When focusing on the undeterminate lesions, the sensitivity and specificity were 75 and 90%, respectively, while the positive and negative predictive values were 82 and 87%, respectively. The specificity and the positive predictive value were higher (100%) when considering the percentage of stained cells. Altogether these results show that galectin-3 constitutes a useful marker in the diagnosis of thyroid lesions classified as undeterminate by conventional cytology.     

甲状腺滤泡癌组织中PD-1和NLRP3表达及其临床意义

目的：探讨甲状腺滤泡癌(FTC)组织中程序性死亡蛋白1(PD-1)和NOD样受体蛋白3(NLRP3)的表达及其与患者临床病理特征和预后的关系。方法：收集2015年1月至2020年6月福建医科大学附属第二医院手术切除的60例FTC患者的癌和配对癌旁组织标本,采用免疫组织化学染色法检测癌及癌旁组织中PD-1和NLRP3的阳性表达率,χ²检验或者Fisher精确检验法分析PD-1和NLRP3表达与FTC患者临床病理特征的关系,Pearson相关性分析PD-1与NLRP3表达的关系,Kaplan-Meier生存和Logistic回归分析PD-1和NLRP3表达与患者预后的关系。结果：在60例FTC组织中,PD-1和NLRP3均有较高的阳性表达率(46.67%与63.33%)。PD-1表达与FTC患者肿瘤分期、肿瘤大小、血管侵犯、复发与否具有显著相关性(均P<0.05),NLRP3表达与患者肿瘤大小、血管侵犯、甲状腺外浸润以及复发具有显著相关性(均P<0.05)。PD-1与NLRP3的表达成负相关,前者与患者更好的预后相关,后者是FTC复发的独立风险因素。结论：...     

大鼠肺鳞癌发生发展中环氧化酶-2和caspase-3的表达和意义

目的 :研究参与炎症的环氧化酶 -2(Cox 2 )和凋亡相关蛋白caspase 3在大鼠肺鳞癌发生发展各阶段的蛋白表达状况并探讨炎症、凋亡和肺癌发生发展的关系。方法 :Wistar大鼠 80只 ,左肺叶支气管灌注含三甲基胆蒽(MCA)和二乙基亚硝胺 (DEN )的碘油溶液 ,分批处死获取肺鳞癌形成过程各阶段标本。免疫组化检测各阶段病变组织Cox 2、caspase 3 的表达并计算免疫组化评分 (IHS)。结果 :79 0 0 %( 4 9/ 62 )的动物标本有多个阶段病变共存 ,共获取支气管膜上皮增生 14例 ,鳞状化生 2 5例 ,不典型增生 3 3例 ,原位癌 12例 ,侵袭癌 5 4例 ,转移癌 17例。正常支气管黏膜上皮偶有Cox 2弱阳性表达 ,随着癌变进展而逐步上调。不典型增生、原位癌及转移癌阶段Cox 2的IHS增高有统计学意义 ,P <0 0 1、P <0 0 5、P <0 0 1。 10例对照组大鼠支气管黏膜上皮细胞中 8例 ( 8/ 10 )有caspase 3的阳性表达 ,随着支气管黏膜上皮的癌变进程表达下降。不典型增生、转移癌阶段caspase 3的HIS降低有统计学意义 ,P <0 0 5、P <0 0 1。在 165例大鼠肺组织病变中 ,Cox 2与caspase 3呈显著负相关 ,χ2 =2 1 675 ,spearman相关系数为 -0 2 46,P =0 0 0 1。结论 :Cox 2、caspase 3均与肺鳞癌的发生和发展过程相关 ,可能是联系炎症、凋     

Expression of sodium iodide symporter in metastatic and follicular human thyroid tissues

Active iodide uptake across the basal membrane mediated by human sodiumiodide symporter (hNIS) has been shown to be a process coupled with the flowof sodium. There is still controversy as to the amount of hNIS expressionpresent in different kinds of human thyroid cancer tissues. In this study, wepresent a 58-year-old women with follicular thyroid carcinoma with vertebraand skull metastases. ²⁰¹Tl and 5 mCi ¹³¹I scans clearlydemonstrated the metastatic lesions in the brain of this patient. Thyroid andmetastatic tissues were then obtained for this study, which is aimed atcomparing the iodide trapping ability in vivo and in vitro of hNIS, and then comparing their expression in both thyroid tissue andmetastatic tissues. Polyclonal antibodies to hNIS and competitive RT–PCRwere used to analyze the symporter protein and mRNA expressed in follicularhuman thyroid and metastatic tissues. Positive staining of the symporterprotein was performed in the follicular thyroid carcinomas, otherwise, themetastatic tissues could not have demonstrated the protein in the staining.Follicular thyroid carcinoma tissues from thyroid were revealed around 5 pghNIS expressed in follicular thyroid carcinoma tissues from the thyroid.Otherwise, there was almost an absence of hNIS expression in the metastatictissue. These discrepancies of the expression in hNIS in vivo and in vitrostudies need further investigation.     

胃癌中survivin和caspase-3的表达及其临床意义

背景与目的：细胞凋亡调控失衡在肿瘤发生发展中具有重要意义,survivin和caspase-3对细胞凋亡和细胞周期调控起着重要作用。本研究通过检测survivin和caspase-3在胃癌组织中的表达,探讨其与胃癌临床病理因素之间的相关性及作用机制。方法：采用RT-PCR及免疫组织化学法分别检测79例不同病理分期的胃癌组织及30例癌旁组织中survivin和caspase-3的表达。结果：caspase-3及survivin mRNA表达与肿瘤的浸润深度、淋巴结转移和TNM分期显著性相关,差异均有统计学意义（P〈0.05）;survivin和caspase-3 mRNA在胃癌组织中的表达差异有统计学意义（P〈0.01）。结论：Survivin、caspase-3的表达与胃癌的发生和发展密切相关, 其作用机制可能是通过survivin分子的高表达而抑制caspase-3的表达,从而抑制胃癌细胞凋亡最终导致胃癌病程的演进。     

Risks of papillary and follicular thyroid cancer among immigrants to Sweden

Previous studies have indicated that ionizing radiation, particularly during childhood, is the main established risk factor for thyroid cancer. History of benign nodules/adenoma, goiter, iodine deficiency or high-iodine intake might be other associated factors. We wanted to define the histology-specific thyroid cancer risk in the first-generation immigrants to Sweden. We used the 2010 update of the nation-wide Swedish Family-Cancer Database (>12 million individuals; 1.8 million immigrants; histology code in force since 1958) to calculate standardized incidence ratios (SIRs) for histology-specific thyroid cancer among immigrants compared to the native Swedes. The patient series covered 2,604 male and 6,406 female Swedes, and 247 and 863 immigrants. The median age at immigration was 29 years, and the median age at thyroid cancer diagnosis was 46 years. Increased risks for female papillary carcinoma were observed for Finns (SIR = 1.63), former Yugoslavians (2.36), Russians (2.34), other East Europeans (2.14), Turks (3.16), Iranians (2.68), Iraqis (2.77), East and Southeast Asians (2.92), other Asians (1.69) and South Americans (2.23). Male Iranians (2.85), East and Southeast Asians (3.57) and other Asians (2.26) had an increased risk for papillary carcinoma. Only male East and Southeast Asians (2.93) had an increased risk for follicular carcinoma. The data might suggest that immigrant populations in Sweden from areas of low or high-iodine intake are at risk of papillary carcinoma, implicating iodine imbalance as a contributing factor to our findings. The increased risk of thyroid cancer among Asian immigrants may confirm the role of childhood-ionizing radiation on thyroid cancer risk.     

CK19、Galectin-3、HBME-1、p27及CyclinD1在甲状腺乳头状癌中的表达及意义

背景与目的:甲状腺乳头状癌的诊断有时会很困难,而淋巴结转移是甲状腺乳头状癌局部复发的主要原因并影响预后.本研究探讨CK19、Galectin-3、HBME-1、p27及CyclinD1在甲状腺乳头状癌中的表达特点和诊断价值以及p27、CyclinD1与乳头状癌淋巴结转移间的关系.方法:收集2005年1月至2008年12月间在我院手术的50例甲状腺良性病变患者 (结节性甲状腺肿40例,甲状腺腺瘤10例)及50例甲状腺乳头状癌(经典型40例,滤泡型10例) 患者的手术标本,用免疫组化EnViSion法检测CK19、HBME-1、Galectin-3、p27及CyclinD1的表达.结果:细胞质或细胞膜均有CK19、Galectin-3和HBME-1三种标志物表达,但p27和CyclinD1则在细胞核表达.CK19、HBME-1、Galectin-3在甲状腺乳头状癌中的表达阳性率分别为100%、96%和100%,而在良性病变中则为10%、10%和6%,两者比较差异有显著性(P<0.01).p27在甲状腺乳头状癌的表达阳性率为14%,而在良性病变中则为84%,两者比较差异有显著性(P<0.01).CyclinD1在甲状腺良、恶性病变中的表达阳性率分别为68%和78%,两者间差异无显著性(P>0.05).在甲状腺乳头状癌患者中,CK19、Galectin-3和HBME-1共同表达者占98%(49/50),其中伴p27低表达者占90%(45/50),而在良性病变者中则分别为2%(1/50)和0%(0/50),前两者与后者之间相比,差异有显著性(P<0.01).p27低表达与CyclinD1表达(转移组阳性率72.7%,未转移组71.4%)与甲状腺乳头状癌淋巴结转移间无显著相关性(P>0.05).结论:联合检测CK19、Galectin-3和HBME-1对甲状腺乳头状癌的诊断与鉴别诊断具有重要价值,而p27的低表达与CyclinD1表达对甲状腺乳头状癌的淋巴结转移无提示作用.     

吉西他滨作用于肝癌HepG2细胞后对DR5、caspase-8、caspase-9和caspase-3表达的影响

目的 研究吉西他滨作用于HepG2细胞后DR5、caspase-8、caspase-9、caspase-3的表达,以期探讨吉西他滨诱导HepG2细胞凋亡的机制.方法 应用MTT法和流式细胞仪体外研究吉西他滨对HepG2细胞增殖的影响;采用免疫细胞化学及Western blot法,观察吉西他滨作用于HepG2细胞24 h后DR5、caspase-8、caspase-9、caspase 3的表达情况.结果 吉西他滨对肝癌HepG2细胞的抑制作用呈时间和浓度依赖性;吉西他滨作用于HepG2细胞24 h后,细胞表面DR5及caspase-8、caspase-9、caspase-3的表达均增强.结论 吉西他滨诱导肝癌HepG2细胞凋亡的机制可能与其能够上调DR5及caspase-8、caspase-9、caspase-3的表达有关.     

乳腺癌caspase-7、caspase-3、survivin的表达及与临床病理因素关系的探讨

目的:探讨乳腺癌中caspase-7、caspase-3、survivin的表达、与临床病理因素的关系及3者间表达强度的相关性。方法:免疫组织化学法检测caspase-7、caspase-3、survivin在45例乳腺癌标本中的表达,并分析其与临床病理因素的关系。结果:caspase-7、caspase-3、survivin表达阳性率分别为73.33%、82.22%、73.33%,3者在年龄、月经状态、淋巴结有无转移各组中阳性率无显著差异,P值均>0.05。3者表达强度与肿块大小、临床TNM分期、组织学分级间,仅见caspse-7表达强度与肿块大小呈负相关(r=-0.306,P=0.041),caspse-7与caspase-3表达强度呈正相关(r=0.307,P=0.040)。结论:caspse-7与肿瘤负荷有关,与caspase-3在乳腺癌细胞凋亡过程中可能起协同作用,survivin在乳腺癌中高表达,3者与临床病理因素的关系需进一步深入研究。     

14-3-3 sigma possibly plays a constitutive role in papillary carcinoma, but not in follicular tumor of the thyroid

14-3-3 σ is a negative regulator of the cell cycle and contributes to G2 arrest. Thus far, the lack of its expression due to hypermethylation of the CpG islands has been reported in some carcinomas. In this study, we investigated the expression of 14-3-3 σ in thyroid neoplasms by means of immunohistochemistry as well as Western blot analysis. Normal follicules did not express 14-3-3 σ. In 82 papillary carcinomas, all the cases expressed 14-3-3 σ and its expression was not reduced but even enhanced in the advanced stage and in poorly differentiated types. Furthermore, 21 of the 23 anaplastic carcinomas expressed 14-3-3 σ and its expression level tended to be higher than in papillary carcinoma. On the other hand, none of the 34 follicular carcinomas or 29 follicular adenomas expressed 14-3-3 σ. These results suggest that 14-3-3 σ plays a constitutive role in papillary carcinoma rather than acting as a cell cycle regulator, whereas it is not required for the occurrence and development of follicular tumor.     

雌激素受体和细胞增殖周期调控蛋白D1在分化型甲状腺癌中的表达及意义

目的:探讨雌激素受体(ER)和细胞增殖周期调控蛋白(cyclinD1)在分化型甲状腺癌(DTC)中的表达及意义。方法:用免疫组织化学SP法研究不同甲状腺组织中ER和cyclinD1的表达。DTC43例(乳头状癌39例,滤泡状癌4例),甲状腺良性腺瘤30例,腺瘤旁正常组织16例。结果:DTC组织中ER和cyclinD1蛋白阳性率分别为53.5%(23/43)、65.1%(28/43);甲状腺良性瘤中ER和cyclinD1蛋白阳性率分别为26.7%(8/30)、36.7%(11/30);正常甲状腺组织中ER阳性率为12.5%(2/16),而cyclinD1则不表达。DTC中ER的表达明显高于甲状腺良性腺瘤和正常甲状腺组织(P<0.05);DTC中cyclinD1的表达明显高于甲状腺良性腺瘤(P<0.05);且DTC中cyclinD1和ER表达存在正相关关系(P<0.05)。结论:雌激素在DTC的发生、发展中有促进细胞增殖的作用;DTC可能为雌激素依赖性肿瘤。     

肝细胞癌survivin和caspase-3的表达及其与预后的关系

目的研究肝细胞癌（HCC）癌组织及癌旁组织survivin、caspase-3的表达及其与患者术后生存率之间的关系。方法免疫组织化学S-P法检测PCNA、survivin、caspase-3的表达,并以PCNA阳性强度计算增殖指数（PCNA-PI）,原位末端转移酶标记（TUNEL）法检测凋亡指数（AI）。结果survivin在肝细胞肝癌中表达阳性率高于癌旁组织（P〈0.05）。其阳性表达与肿瘤大小、肿瘤细胞分化程度、门静脉癌栓有关。癌组织中survivin表达阳性组的增殖指数PCNA-PI高于阴性组（P〈0.05）,凋亡指数低于阴性组（P〈0.05）。caspase-3在肝细胞癌中表达阳性率低于癌旁组织（P〈0.05）;其表达与肿瘤细胞分化程度和HBsAg有关。癌组织中caspase-3表达阳性组的增殖指数PCNA-PI低于阴性组（P〈0.05）,凋亡指数高于阴性组（P〈0.05）。在肝癌组织中survivin与caspase-3的表达呈负相关（r=-0.242,P〈0.05）。survivin阳性组患者生存率低于阴性组（P〈0.05）。caspase-3阴性组患者生存率低于阳性组（P〈0.05）。结论肝细胞癌组织survivin和caspase-3的表达影响癌细胞的增殖凋亡,对于判断HCC预后具有一定价值。