Apaf-1在甲状腺乳头状癌中的表达及意义

目的:探讨凋亡蛋白酶活化因子1(Apaf-1)在甲状腺乳头状癌(PTC)中的m RNA与蛋白表达及其与细胞增殖的关系。方法:分别采用real-time PCR、Western blot及免疫组化法检测并比较甲状腺乳头状癌和癌旁组织中Apaf-1的m RNA及蛋白表达情况,并分析其表达水平与PTC临床病理学特征的关系;通过下调CGTHW-3细胞中Apaf-1表达量,验证Apaf-1对细胞增殖的影响。结果:在PTC组织中,Apaf-1的m RNA和蛋白表达量均显著低于癌旁组织(P 0. 05);下调Apaf-1表达增强了CGTHW-3细胞的增殖活性(P 0. 05)。结论:Apaf-1在PTC中低表达,抑制其表达可增强CGTHW-3细胞的增殖能力。Apaf-1在甲状腺乳头状癌中可能发挥抑癌作用。     

核仁素在甲状腺乳头状癌中表达的临床意义

目的 探讨核仁素（NCL）在甲状腺乳头状癌中的表达及临床意义。方法 采用免疫组织化学SP染色法检测60例正常甲状腺组织与甲状腺乳头状癌中NCL、趋化因子受体-7（CCR7）与基质金属蛋白酶-9（MMP-9）的表达,分析NCL、CCR7与MMP-9的表达与性别、年龄、肿瘤大小与
有无转移的关系以及核仁素与CCR7、MMP-9表达的相关性。结果 NCL在正常甲状腺及甲状腺乳头状癌中的总阳性率分别为0、 100%。NCL在伴随转移组癌组织中表达于细胞核、细胞质与细胞膜;NCL在无转移组癌组织中仅表达于细胞核,差异有统计学意义（P<0.05）。不同年龄、性别、
肿瘤大小的NCL表达率间的差异无统计学意义(P>0.05)。核仁素细胞核外阳性表达与CCR7与MMP-9的阳性表达呈正相关（P<0.01）。结论 NCL在甲状腺乳头状癌中表达,表达部位在转移与非转移组明显不同,且与CCR7、MMP-9表达有密切关系。核仁素可作为区别癌转移与非转移的标志。     

SUMO4在甲状腺乳头状癌中的表达及临床意义

目的:探讨小泛素相关修饰因子4(SUMO4)表达与甲状腺乳头状癌(PTC)发生发展的关系。方法:采用real-time PCR、Western blot及免疫组化等方法检测PTC和正常甲状腺组织中SUMO4的mRNA及蛋白表达情况,对比研究SUMO4蛋白表达与PTC及其临床病理特征的关系。结果:SUMO4的mRNA及蛋白表达量在PTC中均明显高于正常甲状腺组织(P0.01)。结论:SUMO4在PTC的高表达提示其在PTC发生发展中扮演着重要的角色,可能与PTC发病的分子机制有关。     

胃腺癌预后评估中Tiam1蛋白过表达的意义

目的探讨T淋巴瘤转移诱导因子1(T-cell lymphoma invasion and metastasis-inducing factor 1,Tiam1)过表达在胃腺癌(gastric adenocarcinoma,GAC)临床预后评估中的意义。方法采用免疫组化En Vision法检测Tiam1蛋白在102例GAC组织、21例胃异型增生组织和33例癌旁正常组织中的表达,并分析其过表达与GAC患者预后之间的关系。结果 GAC组织中Tiam1阳性率为85.3%(87/102),强阳性率为61.8%(63/102),均明显高于胃异型增生组织和癌旁正常组织(P均0.01)。Tiam1蛋白表达水平与GAC分化程度、临床分期、淋巴结转移及浆膜浸润密切相关(P均0.05),与患者性别、年龄及肿块大小等均无关。结论 Tiam1蛋白表达水平与GAC的发生、发展及预后密切相关,Tiam1蛋白过表达可成为GAC患者不良预后的重要指标之一。     

Prognostic value of morphometry in papillary thyroid carcinoma

The value of morphometric analysis in addition to standard prognostic indicators was studied in 28 cases of papillary thyroid carcinoma. Standard features included age, sex, lymph node status, tumor size, and encapsulation. The mean follow-up was 47 months (maximum, 140 months). Recurrences were documented in six patients at a mean time of 34 months; five patients recurred with distal metastases and one patient recurred with local disease. Univariate analysis most closely associated tumor recurrence with nuclear anisotropism (the standard deviation of the estimated nuclear area [ENASD]) and tumor size. With forward stepwise incremental analysis, the value of tumor size was lost and only the ENASD and the cellularity mean index (CMI), defined as the percentage of tumor volume composed of tumor cells, significantly correlated with recurrence. Fifty-five percent of patients with an ENASD greater than 17 microns2 and a CMI greater than 40% developed recurrence as compared with 5% of patients with lesser values (P = .0001). Morphometric analysis may significantly contribute to the role of histopathology in the evaluation of papillary thyroid carcinoma and may also provide information regarding prognosis not obtained by standard methods.     

Prognostic significance of Leu-M1 immunostaining in papillary carcinomas of the thyroid gland

Summary Leu-M1 antigen is a monocyte/granulocyte-related marker known to be consistently expressed in the Reed-Sternberg cells of patients with Hodgkin's disease. Recently, however, the presence of Leu-M1 has also been noted in tumour cells of a variety of non-haematopoietic neoplasms, most of them adenocarcinomas. The biological significance of this aberrant reaction has not been clarified. We have been able to demonstrate marked epithelial Leu-M1 immunoreactivity (>15% tumour cells positively stained) in 24 out of 76 (32%) papillary carcinomas of the thyroid gland (PC). This phenomenon was more frequently observed among PCs at an advanced stage of disease (pT₄ vs. pT_1–3 and M₁ vs. M₀ p<0.05). The degree of epithelial Leu-M1 positivity was also shown to be significantly correlated to the clinical course of PC. Irrespective of other morphological and clinical features, death resulting from cancer occurred 17 times more frequently among PCs with marked Leu-M1 positivity (8/24) when compared with tumours with only slight or absent immunoreactivity (1/52) (p<0.00005). These findings suggest that Leu-M1 immunostaining provides significant prognostic information for patients with papillary carcinoma of the thyroid gland.     

甲状腺乳头状癌中TROP-2表达的临床意义及其诊断价值

目的观察人类滋养层细胞表面抗原2(TROP-2)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)中的表达,探讨TROP-2在PTC中表达的临床意义及其诊断价值。方法采用免疫组化EnVision法检测100例甲状腺恶性病变(PTC 75例、滤泡性癌10例、髓样癌10例、差分化癌5例)、45例良性病变(正常甲状腺10例、结节性甲状腺肿10例、桥本甲状腺炎15例、滤泡性腺瘤10例),5例具有乳头样核特征的非浸润性甲状腺滤泡性肿瘤(non-invasive folliculaRthyroid neoplasms with papillary-like nucleaRfeatures,NIFTP)中TROP-2的表达;ARMS法检测PTC中BRAF V600E基因突变。分析TROP-2对PTC诊断的敏感性和特异性,及其与PTC临床病理特征以及BRAF V600E基因突变的关系。结果TROP-2在PTC中的阳性率为81.3%(61/75),在其他甲状腺恶性肿瘤和良性病变中均阴性,TROP-2对PTC诊断的敏感性为81.3%,特异性为100%。TROP-2表达与PTC淋巴结转移有关(P<0.05),与患者年龄、性别、肿瘤部位及临床分期无关(P>0.05),经典型PTC中TROP-2表达高于滤泡亚型PTC(P<0.05)。PTC中TROP-2表达与BRAF V600E基因突变呈正相关(P<0.05)。结论TROP-2是一种具有高度特异性和敏感性的诊断PTC的标志物,TROP-2检测可预测PTC的临床生物学行为和BRAF V600E基因突变状态,并对于形态学变形的PTC、微小型PTC和PTC的甲状腺内扩散的诊断和识别具有重要价值。     

BRAF基因突变在甲状腺乳头状癌中的临床意义

目的：探讨BRAF V600E基因突变与甲状腺乳头状癌的临床相关性。方法：采用PCR技术和直接测序法,对63例甲状腺乳头状癌患者和45例其他类型甲状腺疾病患者石蜡组织BRAF V600E基因突变进行检测。结果：甲状腺乳头状癌组中32例存在突变;而在其他类型甲状腺疾病组中未发现突变。BRAF V600E基因突变在甲状腺乳头状癌不同肿瘤直径组之间的比较差异以及在有无区域淋巴结转移组之间的比较差异均具有统计学意义(P<0.05)。结论：BRAF V600E基因突变与甲状腺乳头状癌的发生、肿瘤的大小和区域淋巴结的转移有关。     

Expression of PPM1D in papillary carcinoma of thyroid and its significance

目的 探讨甲状腺乳头状癌(papillary carcinoma of thyroid,PTC)中PPM1D蛋白的表达情况及其与临床病理特征和p53的关系.方法 应用免疫组化EnVision法检测55例PTC及癌旁正常组织中PPM1D蛋白的表达情况并进行统计处理,分析其与临床病理特征的关系及和p53蛋白表达的相关性.结果 55例PTC中PPM1D的表达(74.5%,41/55)高于癌旁正常组织(10.9%,6/55),差异有统计学意义;PPPM1D的表达与患者年龄、性别、肿瘤大小、组织学类型、淋巴结转移、TNM分期无关,而在间质硬化的病例中表达增强(P＜0.05);PTC中PPM1D与p53蛋白表达呈负相关(r=-0.339,P＜0.05).结论 高表达的PPM1D与PTC相关,与p53之间可能存在相互作用,在PTC发生、发展中具有重要意义.     

甲状腺乳头状癌中PPM1D的表达和意义

目的探讨甲状腺乳头状癌(papillary carcinoma of thyroid,PTC)中PPM1D蛋白的表达情况及其与临床病理特征和p53的关系。方法应用免疫组化EnVision法检测55例PTC及癌旁正常组织中PPM1D蛋白的表达情况并进行统计处理,分析其与临床病理特征的关系及和p53蛋白表达的相关性。结果 55例PTC中PPM1D的表达(74.5%,41/55)高于癌旁正常组织(10.9%,6/55),差异有统计学意义;PPPM1D的表达与患者年龄、性别、肿瘤大小、组织学类型、淋巴结转移、TNM分期无关,而在间质硬化的病例中表达增强(P<0.05);PTC中PPM1D与p53蛋白表达呈负相关(r=-0.339,P<0.05)。结论高表达的PPM1D与PTC相关,与p53之间可能存在相互作用,在PTC发生、发展中具有重要意义。     

Intranodal benign thyroid tissue: significance of HBME-1 in differentiation from metastatic papillary thyroid carcinoma

The aim of this study was to determine the significance of HBME-1 immunostaining in the differentiation between intranodal benign thyroid tissue and metastatic papillary thyroid carcinoma in the lymph node. Immunohistochemically we examined normal-appearing intranodal thyroid tissue in four patients who did not show evidence of papillary carcinoma histologically or clinically. We also examined follicular-pattern-predominant papillary carcinoma with metastatic foci in the lymph nodes. Normal-appearing intranodal thyroid tissue and normal thyroid showed no immunopositivity for HBME-1. In contrast, all papillary carcinomas in both the lymph nodes and thyroid demonstrated strong positivity for HBME-1. HBME-1 was predominantly positive for the luminal surface of the tumor cells. The immunopositivity of the cuboidal and low columnar carcinoma cells was more intensive than that of the flat-shaped cells in the lymph nodes and thyroid. The results probably indicate that HBME-1 immunostaining is helpful in distinguishing between intranodal benign thyroid tissue and metastatic papillary carcinoma in lymph nodes. We emphasize that the HBME-1 reactivity should be evaluated in connection with the histological findings, and that positive and negative controls stained in parallel are necessary.     

VDR在甲状腺乳头状癌中的表达及临床意义

目的检测维生素D受体(vitamin D receptor,VDR)在甲状腺乳头状癌中的表达及定位,分析VDR与CK19、HMBE-1、Galectin-3、CD56及TPO蛋白的表达相关性,探讨甲状腺乳头状癌中VDR的表达及其临床意义。方法应用免疫组织化学染色方法检测VDR在98例甲状腺乳头状癌及其癌旁组织中的表达及定位,同时用Western blot验证VDR在甲状腺乳头状癌和癌旁组织中的蛋白表达,应用SPSS23.0统计分析VDR与CK19、HMBE-1、Galectin-3、CD56及TPO蛋白的表达相关性。结果 VDR在甲状腺乳头状癌中表达增高,定位于细胞质, VDR的表达与Galectin-3的表达呈显著负相关,而与患者年龄、性别、肿瘤直径大小、临床分期、淋巴结转移无显著相关性(P0.01),与CK19、HMBE-1、CD56及TPO的表达无显著相关性。结论 VDR可能是甲状腺乳头状癌中Galectin-3表达的重要调节因子,VDR可作为靶向治疗的潜在生物靶点。     

血管内皮生长因子-C和血管内皮生长因子受体-3在侵袭性甲状腺乳头状癌中的表达及意义

目的 观察血管内皮生长因子(VEGF-C)和血管内皮生长因子受体(VEGFR3)在侵袭性甲状腺乳头状癌组织中的表达,探讨甲状腺乳头状癌细胞淋巴管转移机理.方法 用免疫组化方法检测VEGF-C和VEGFR3在人侵袭性甲状腺乳头状癌和非侵袭性甲状腺乳头状癌中的表达情况,并进行比较和分析.结果 在侵袭性和非侵袭性甲状腺乳头状癌中均可见到VEGF-C和VEGFR3阳性表达,但在侵袭性甲状腺乳头状癌组织VEGF-C (x2=4.738,P=0.030)和VEGFR3(x2=11.951,P=0.010)的表达率和表达强度均高于非侵袭性甲状腺乳头状癌.结论 VEGF-C和VEGFR3在侵袭性甲状腺乳头状癌细胞中高表达,并且可能与此肿瘤的侵袭性相关.     

p27kip1 expression distinguishes papillary hyperplasia in Graves' disease from papillary thyroid carcinoma.

In most cases, the histopathologic and cytologic distinction between Graves' disease and papillary thyroid carcinoma is relatively easy, but on occasion Graves' disease may simulate a thyroid papillary carcinoma. For example, papillary fronds with fibrovascular cores may be present in both Graves' disease and papillary carcinoma. p27kip1 (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic factor in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distinction could also be made between Graves' disease and papillary carcinoma, we analyzed expression of p27 and other cell cycle proteins in a series of cases of Graves' disease with papillary hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randomly selected patients with thyroid disease, including 29 cases of Graves' disease with papillary architectural features and 32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II alpha (topo II alpha) by immunostaining. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/- 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2.5 (range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II alpha expression were identified between papillary hyperplasia in Graves' disease and papillary carcinoma. These results indicate that p27 protein expression is significantly higher in papillary hyperplasia of Graves' disease compared to papillary carcinoma, which may be diagnostically useful in difficult cases.     

TROP‐2 expression in papillary thyroid carcinoma

TROP‐2 is a type I transmembrane glycoprotein which is over‐expressed in various malignancies, and is related to epithelial cell adhesion molecule (EpCAM), also called TROP‐1, gp40, and KSA. In this study, we evaluated TROP‐2 expression in papillary thyroid carcinoma (PTC) and compared it to other thyroid neoplastic and non‐neoplastic lesions. Immunohistochemical (IHC) evaluation for TROP‐2 was performed on 137 thyroid fine needle aspiration (FNA) cell blocks (CB) which included classic PTC (64), follicular variant PTC (FVPTC) (10), anaplastic thyroid carcinoma (AC) (2), medullary carcinoma (MC) (8), follicular neoplasms (FN) (8), Hurthle cell neoplasms (HCN) (9), follicular lesion of uncertain significance (FLUS) (12), and benign thyroid nodule (BTN) (24). IHC for TROP‐2 expression was also performed on 331 BTN and malignant tumor tissue sections in tissue microarray (TMA). Membranous staining in >5% of tumor cells was considered positive. TROP‐2 stained 61 of 64 PTC CB, 7 of 10 FVPTC CB, and 9 of 12 FLUS CB. All other cases were negative for TROP‐2. TROP‐2 showed a sensitivity of 95.31% and specificity of 89% for classic PTC in FNA CB. In TMA samples, TROP‐2 stained 54 of 60 classic PTC cases and hence showed a high sensitivity and specificity. All BTN in CB and TMA were negative. We conclude that TROP‐2 is a highly sensitive and specific IHC marker for identifying classic PTC. TROP‐2 may play an important role in diagnosing classic PTC, especially in equivocal cases. This study also identifies a strong role for TROP‐2 in separating PTC from BTN. Diagn. Cytopathol. 2016;44:26–31. © 2015 Wiley Periodicals, Inc.     

甲状腺乳头状癌中BRAF基因的表达及意义

目的探讨BRAF基因突变与甲状腺乳头状癌(papillary thyroid carcinoma,PTC)及其临床病理特征之间的关系。方法采用免疫组化EnVision两步法、巢式PCR和基因测序法检测107例甲状腺石蜡包埋组织中BRAF点突变情况(包括93例PTC、5例滤泡癌、1例髓样癌、8例甲状腺腺瘤)。结果 93例PTC中,BRAF蛋白阳性者69例,阳性率为74.2%(69/93),BRAF蛋白对照组中仅有1例滤泡癌阳性表达(20%),而8例甲状腺腺瘤和1例髓样癌中BRAF蛋白均阴性表达。在PTC中检测到BRAF基因突变,突变率为32.3%(30/93),在其它类型的甲状腺病变中均未检测到BRAF基因突变。93例PTC的临床病理资料与BRAF蛋白表达及基因突变的对比分析显示,45岁以下患者的BRAF基因突变率高于45岁以上者,肿瘤直径>1 cm的患者BRAF基因突变率高于肿瘤直径<1 cm患者,差异具有统计学意义(P<0.05),而BRAF蛋白表达和基因突变、性别、淋巴结转移、血管内瘤栓和腺外浸润等无相关性。结论 BRAF基因突变仅发生在PTC中,其可能对PTC的诊断、治疗及预后判定提供新的理论依据。     

Clinical significance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma

AIMS: Rearranged during Transfection (RET)/papillary thyroid carcinoma (PTC) and p53 are two genes involved in the pathogenesis of PTC. It has been suggested that RET/PTC expression is associated with higher rates of local extension and lymph node involvement, whereas p53 mutations are more frequent in poorly differentiated and anaplastic carcinomas. In addition, experimental studies have shown that p53 activity can modify the behaviour of PTC carrying RET/PTC. The aim of this study was to investigate the expression of both RET/PTC and p53 in order to evaluate their usefulness as prognostic factors. METHODS AND RESULTS: Resected specimens of 61 cases of PTC were studied immunohistochemically using a polyclonal antibody to RET and a monoclonal antibody to p53 protein. RET/PTC expression was associated with extrathyroid extension of PTC, at diagnosis (P < 0.05). In contrast, no relationship between p53 immunoreactivity and clinical status was found. In addition, p53 expression was more prevalent among RET/PTC+ patients, and significantly influenced the relationship observed between RET/PTC and extrathyroid extension of the disease. CONCLUSION: Our results suggest that immunohistochemistry for both PTC/RET and p53 could be useful in the clinical evaluation of patients with PTC.     

Smad4在甲状腺乳头状癌组织中的表达及临床意义

目的 探讨Smad4在甲状腺乳头状癌组织中的表达水平及其意义.方法 选取31例甲状腺乳头状癌组织作为实验组,17例甲状腺良性病变组为对照组.应用免疫组织化学方法检测两组Smad4的阳性表达率,Western blot方法检测两组Smad4的表达水平;实时荧光定量PCR方法检测两组Smad4 mRNA的表达水平.结果 甲...