CK19,S-100和EMA在鉴别甲状腺乳头状癌与乳头状增生中的作用

目的：评估检测CK19、S-100蛋白和EMA在诊断甲状腺乳头状癌、滤泡性癌及乳头状增生中的作用。方法：65例甲状腺病变组织分别用CK19、S-100、EMA进行免疫组化染色。结果：在乳头状增生中，CK19、S-100和EMA均不表达。CK19在乳头状癌包括滤泡型乳头状癌中100％表达，在滤泡性癌中有22％的表达。S-100和EMA在经典型乳头状癌分别为61％、100％；滤泡型乳头状癌38％、54％和滤泡性癌44％，11％。结论：CK19结合S-100和EMA检查在诊断甲状腺病变中是有用的辅助手段。CK19在区分甲状腺乳头状癌和乳头状增生中是一个很好的标志物。     

桥本甲状腺炎合并甲状腺癌患者肿瘤内抗肿瘤免疫临床意义

目的 观察桥本甲状腺炎合并甲状腺癌患者肿瘤内抗肿瘤免疫并探讨其临床意义.方法 应用免疫组织化学二步法检测桥本甲状腺炎合并甲状腺乳头状癌患者肿瘤组织内S-100蛋白呈阳性的树突状细胞及HLA-DR抗原呈阳性表达的细胞并探讨其临床意义.结果 桥本甲状腺炎合并甲状腺乳头状癌患者肿瘤组织内存在大量树突状细胞(8/8),数量明显多于不伴桥本甲状腺炎的甲状腺癌患者(1/20),树突状细胞的胞浆突起插入癌细胞之间并与之接触.癌细胞呈不同程度HLA-DR抗原阳性表达.在树突状细胞及HLA-DR抗原阳性表达的癌细胞间可见大量淋巴细胞围绕.癌细胞存在不同程度坏死、崩解、脱落.结论 桥本甲状腺炎合并甲状腺乳头状癌患者肿瘤组织内存在由树突状细胞、淋巴细胞及HLA-DR抗原阳性表达的癌细胞引起的特异性抗肿瘤免疫,与患者预后可能密切相关.     

S100A4 expression is an early event of papillary carcinoma of the thyroid

OBJECTIVES: S100A4 is a calcium-binding protein related to the metastatic potential of carcinoma. In order to elucidate its contribution to the progression of thyroid carcinoma, we investigated S100A4 expression in various thyroid neoplasms. METHODS: We immunohistochemically examined S100A4 expression in 195 cases of thyroid neoplasms. RESULTS: Although S100A4 was absent in normal follicular cells and follicular adenoma, S100A4 was positive in all 115 cases of papillary carcinoma examined, including 58 microcarcinomas. However, a significant relationship could not be established between S100A4 expression and clinicopathological features of papillary carcinoma. In follicular carcinoma, the widely invasive type expressed S100A4 more frequently than the minimally invasive type (p = 0.0028). In anaplastic carcinoma, S100A4 was expressed in 61.9% of cases, but the incidence was significantly lower (p < 0.0001) than that in papillary carcinoma. CONCLUSIONS: These findings suggest that (1) S100A4 plays a constitutive role in papillary carcinoma and (2) S100A4 may be a useful marker for early the detection of this carcinoma.     

AnnexinⅡ、S100A4在甲状腺乳头状癌中的表达及意义

目的探讨甲状腺乳头状癌中钙磷脂结合蛋白Ⅱ（AnnexinⅡ）与钙结合蛋白S100A4的表达,分析其与甲状腺乳头状癌发生及淋巴结转移的关系以及二者的相关性。方法应用免疫组织化学SP法和原位杂交技术检测50例甲状腺乳头状癌组织、14例甲状腺腺瘤组织、26例结节性甲状腺肿组织和10例正常甲状腺组织中AnnexinⅡ、S100A4蛋白和AnnexinⅡmRNA的表达。结果甲状腺乳头状癌中AnnexinⅡ、S100A4蛋白和AnnexinⅡmRNA的阳性表达率分别为82.00%(41/50)、78.00%(39/50)和74.00%(37/50),均明显高于甲状腺腺瘤组织、结节性甲状腺肿组织及正常甲状腺组织(P＜0.05); 三者在癌组织中的表达与甲状腺乳头状癌淋巴结转移有关(P<0.05);AnnexinⅡ蛋白与S100A4蛋白的表达呈正相关性(r=0.380,P=0.025);AnnexinⅡ蛋白与AnnexinⅡmRNA的表达呈正相关性(r=0.434 , P=0.008)。结论AnnexinⅡ蛋白、AnnexinⅡmRNA及S100A4蛋白的高表达与甲状腺乳头状癌的发生和淋巴结转移密切相关,二者联合检测有助于鉴别甲状腺良恶性病变,并预测肿瘤的发展和预后。     

甲状腺乳头状癌组织中S100A14与LOXL2的表达及临床意义

目的 探讨钙结合蛋白S100A14与赖氨酰氧化酶(LOXL)2在甲状腺乳头状癌(PTC)中的表达及临床意义.方法 收集90例甲状腺病变组织蜡块,制成组织芯片,用免疫组织化学法分别检测S100A14与LOXL2蛋白在30例结节性甲状腺肿组织(NG)、30例经典型甲状腺乳头状癌(CPTC)组织及30例高侵袭性甲状腺乳头状癌...     

P-GP170、LRP与Ki-67在甲状腺乳头状癌中的表达及临床意义

 目的　检测多药耐药基因蛋白P 糖蛋白 (P GP170 )和肺耐药蛋白 (LRP)与抗核抗体Ki 6 7在甲状腺乳头状癌中的表达及临床意义。方法　采用免疫组化SP法检测P GP170、LRP、Ki 6 7在 6 4例甲状腺乳头状癌和 2 0例甲状腺腺瘤中的表达。结果　 3种抗体在甲状腺乳头状癌中均呈高表达 ,在甲状腺腺瘤中呈低表达。与甲状腺腺瘤相比有显著性差异 (P <0 .0 1)。P GP170、LRP、Ki 6 7三者呈显著相关性 (LRP与Ki 6 7r =0 .4 2 ,LRP与P GP170r =0 .4 2 ,Ki 6 7与P GP170r =0 .6 5 ,P <0 .0 1)。结论甲状腺乳头状癌标记指数高、耐药性强、化疗敏感性低。在化疗中同时给予耐药抑制剂 ,可以提高化疗敏感性和化疗效果。     

甲状腺乳头状癌组织REGγ、p21的蛋白表达及意义

目的研究REGγ和p21在甲状腺乳头状癌组织和正常甲状腺组织中的表达及相互关系。方法标本取自20例甲状腺乳头状癌组织,10例正常甲状腺组织。Western blot检测甲状腺乳头状癌组织和正常甲状腺组织中REGγ和p21蛋白的表达。结果Western blot检测显示,甲状腺乳头状癌组织的REGγ表达明显高于正常甲状腺组织（P<0.05）,甲状腺乳头状癌组织的p21表达明显低于正常甲状腺组织（P<0.05）。相关性分析显示,甲状腺乳头状癌组织REGγ和p21表达之间程显著的负相关关系（P<0.05）。结论REGγ蛋白的高表达和p21蛋白的低表达与甲状腺乳头状癌的形成有关,甲状腺乳头状癌组织中REGγ可能促进p21蛋白的降解。     

An immunohistochemical study of epithelial membrane antigen, cytokeratin, and vimentin in papillary thyroid carcinoma. Recognition of lethal and favorable prognostic types.

METHODS. Immunoreactivity for epithelial membrane antigen (EMA), cytokeratin, and vimentin was investigated in 15 papillary thyroid carcinomas (PTC) with distant metastases, 25 PTC without distant metastases, and 34 occult PTC without distant metastases that were found incidentally at autopsy. RESULTS. More than 50% of the tumor cells were positive for EMA in 7 (47%) of 15 PTC with distant metastases, 0 (0%) of 25 PTC without distant metastases, and 1 (3%) of 34 occult PTC. The incidence of EMA positivity in PTC with distant metastases was significantly different from that of both PTC without distant metastases and occult PTC (P < 0.001). Cytokeratin reactivity was similar in the three groups, and almost all PTC stained strongly for cytokeratin. Concerning vimentin positivity, there were no significant differences in three groups; however, PTC with distant metastases tended to stain more weakly or focally than PTC without distant metastases or occult PTC. CONCLUSIONS. These results suggest that EMA reactivity may be a useful factor for anticipating the individual risk of distant metastasis or death from PTC at the time of initial surgical treatment.     

Estrogen Receptor- and Progesterone Receptor-Positive Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: A Case Report

The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a relatively rare tumor. We herein report the case of young woman with DSV-PTC who developed cervical lymph node recurrence 7 years after the initial surgery. A 15-year-old female patient with no medical or family history of thyroid tumors developed a thyroid neoplasm in the right lobe. Right thyroidectomy and regional lymphadenectomy were performed, and the tumor was diagnosed as DSV-PTC. She was followed up as an outpatient. Seven years after the surgery, cervical lymph node recurrence developed. On microscopic examination, the thyroid tumor showed a papillary growth pattern with numerous psammoma bodies and distinct fibrosis. Immunohistochemically, the tumor cells were estrogen receptor and progesterone receptor positive with reduced membranous expression of E-cadherin and were intermingled with S-100-positive dendritic/Langerhans cells. DSV-PTC is characterized by a strong tendency for invasion and metastasis. Thus, accurate diagnosis is clinically important, and a morphological and immunohistochemical understanding of DSV-PTC is necessary.Key words: Diffuse sclerosing variant of papillary thyroid carcinoma, Estrogen receptor, Progesterone receptor, E-cadherin, S-100, Immunohistochemistry     

甲状腺乳头状癌与乳头状增生的病理研究

  目的 探讨Galectin3，CK19及Ki-67在甲状腺乳头状癌与乳头状增生中的表达，寻找有助于两者鉴别诊断的标志物。方法 运用免疫组化方法检测100例甲状腺乳头状癌、100例良性乳头状增生中Galectin3，CK19及Ki-67的表达。结果 Galectin3，CK19及Ki-67在甲状腺乳头状癌阳性表达率分别为100 %，97 %及93 %，而在乳头状增生中表达率分别为13 %，30 %及1 %，3种蛋白在乳头状癌与良性乳头状增生间差异有统计学意义（P＜0.05）。在乳头状癌中2种或3种蛋白同时阳性表达为94.3 %，而乳头状增生为0。结论 Galectin3，CK19及Ki-67是鉴别诊断甲状腺乳头状癌与乳头状增生的有用标志物，尤其联合使用更有价值。     

Divergent effects of cytokines on human leukocyte antigen-DR antigen expression of neoplastic and non-neoplastic human thyroid cells.

Apparently complex modulatory effects of alpha-interferon (alpha-IFN), tumor necrosis factor (TNF), and epidermal growth factor (EGF) have been found in neoplastic human thyroid cells, which could possibly affect the final outcome in neoplastic disease. This was achieved by examining the influence of alpha-IFN, TNF, and EGF alone and in combination, on human leukocyte antigen-DR (DR) antigen expression and viability of neoplastic and non-neoplastic human thyroid cells in culture. alpha-IFN-induced DR antigen expression on non-neoplastic human thyroid cells, whereas TNF-alpha or EGF alone were ineffective. The addition of the same TNF-alpha concentrations (10 to 100 ng/ml) to alpha-IFN enhanced the expression of DR antigens compared with the effect of alpha-IFN alone. However, EGF inhibited alpha-IFN-induced DR on the same cells and at the same concentrations (10 to 500 ng/ml) at which the growth factor alone was ineffective. In contrast to the common pattern of cytokine effects on DR expression of all nonmalignant thyroid cell lines, neoplastic thyroid cell lines showed divergent responses to alpha-IFN, TNF-alpha, and EGF. In three malignant thyroid cell lines that were DR negative (follicular carcinoma WRO 82-1 and NRO 87-1 cell lines, and anaplastic carcinoma ARO 81-1), DR antigen could be induced by alpha-IFN and enhanced by TNF-alpha, whereas EGF was ineffective. In a fourth cell line (an anaplastic carcinoma SW1736) alpha-IFN, TNF-alpha, and EGF alone were capable of inducing DR, and a combination of either TNF-alpha and EGF with alpha-IFN potentiated DR induction. In a fifth neoplastic cell line (papillary carcinoma, NPA) that constitutively expressed surface DR, its expression was inhibited by both alpha-IFN and TNF-alpha and was not affected by EGF.     

Expression and distribution of S-100, CD83, and costimulatory molecules (CD80 and CD86) in tissues of thyroid papillary carcinoma

A higher expression of S-100 in tissue of thyroid papillary carcinoma (TPC) vs. thyroid follicular adenoma (TFA) (p < .001) was observed as well as a higher expression of CD83 in the peri-cancerous tissues vs. TFA (p < .001), oppositely, CD83 was negative in the cancerous net. TPC showed greater decreases in levels of CD80 and CD86 than did the TFA. These findings suggest that impaired immune function, absence of CD83-positive mature and activated dendritic cells in cancer nodules may have a role in the pathogenesis of TPC. The low expression of CD80 and CD86 in TPC may help them evade the immune system.     

炎症因子C反应蛋白在甲状腺乳头状癌患者血清中表达的临床意义

目的:研究炎症因子C反应蛋白在甲状腺乳头状癌患者血清中的表达及与临床病理因素的关系。方法:回顾性分析安徽医科大学宿州临床学院耳鼻咽喉-头颈外科与肿瘤外科2015年1月至2018年2月收治的100例甲状腺乳头状癌患者临床资料,测定C反应蛋白在其血清中的表达情况。并分析其表达情况与甲状腺癌临床病理因素之间的关系。结果:C反应蛋白在甲状腺乳头状癌患者血清中表达较高,与对照组相比差异显著。单因素分析中C反应蛋白与肿瘤大小、淋巴结转移等有相关性,差异有统计学意义;与性别、年龄、肿瘤个数无相关性,差异无统计学意义;Logistic回归分析也显示同样结论。结论:炎症因子C反应蛋白表达在甲状腺乳头状癌患者血清中表达较高,并间接提示患者局部复发和预后,值得临床推荐。     

甲状腺乳头状癌中D2-40、EGFR和VEGF的表达及BRAF基因突变

目的 探讨甲状腺乳头状癌中D2-40、表皮生长因子受体(epidermal growth factor receptor,EGFR)及血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达与鼠类肉瘤滤过性毒菌致癌同源体B1(v-raf murine sarcoma viral oncogene homolog B1,BRAF)基因突变及其临床意义.方法选取87例甲状腺乳头状癌和48例甲状腺乳头状增生手术切除标本,应用扩增阻碍突变系统(amplification refractory mutation system,ARMS)及免疫组织化学法检测甲状腺乳头状癌和乳头状增生中BRAF基因突变情况和D2-40、EGFR及VEGF蛋白表达情况.结果甲状腺乳头状癌中BRAF基因突变率与D2-40、EGFR和VEGF蛋白阳性表达率均高于甲状腺乳头状增生(均P＜0.05).甲状腺乳头状癌有淋巴结转移组BRAF基因突变率和D2-40、EGFR及VEGF蛋白阳性表达率均高于无淋巴结转移组(均P＜0.05).结论BRAF突变检测联合D2-40、EGFR及VEGF检测可以提高甲状腺乳头状癌的确诊率,并可能是预测甲状腺乳头状癌淋巴结转移与否的重要指标.     

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.     

Oncocytic carcinoma arising in submandibular gland with immunohistochemical observations and review of the literature

We report a case of oncocytic carcinoma arising in submandibular gland. The tumour occurred in the left submandibular gland of an 82-year-old Japanese man. Histologically, the tumour was mostly composed of large cells with eosinophilic granules in the cytoplasm and they were arranged in the solid sheets, islands with duct-like structure and cords. The tumour cells had aggressively invaded muscles and perineural tissues, and cervical lymphatic metastasis was frequently observed. Histochemically, the tumour cells were strongly positive for phosphotungstic acid-hematoxylin (PTAH) stain, and we diagnosed this malignant tumour as oncocytic carcinoma. Immunohistochemically, the tumour cells reacted positively for cytokeratin 7, 8, 19, epithelial membrane antigen (EMA), alpha-1-antichymotrypsin and carcinoembryonic antigen (CEA), but negative for cytokeratin 13, 14, smooth muscle actin (HHF35) and S-100 protein (S-100). Tumour was diagnosed as oncocytic carcinoma in submandibular gland. Its characteristics are discussed in term of its histopathological and immunohistochemical features.     

Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid carcinoma cell lines and tissues

We used subtractive library screening to identify the changes that occur in gene expression during thyroid cell neoplastic transformation. Complementary DNA from normal thyroid cells (HTC 2) was subtracted from a complementary DNA library constructed from a human thyroid papillary carcinoma cell line. The library was screened for genes upregulated in human thyroid papillary carcinoma cell line cells, and several cDNA clones were isolated. One of these clones has a sirtuin core and high homology with the human silent information regulator protein family. This clone, designated "SIR-T8", was overexpressed in human thyroid carcinoma cell lines and tissues, but not in adenomas. The human SIR-T8 protein has a molecular weight of 39 kDa and is primarily located in the cytoplasm under the nuclear membrane. The SIR-T8 gene is located on chromosome 17q25-1.     

Fascin蛋白在甲状腺乳头状癌中的表达及其临床意义

目的 通过检测Fascin蛋白在正常甲状腺组织、甲状腺良性病变及甲状腺乳头状癌中的表达水平,探讨该蛋白对甲状腺癌诊断和治疗的意义。方法 应用免疫组织化学方法,检测60例甲状腺乳头状癌(其中23例伴有淋巴结转移)、40例甲状腺良性肿瘤(甲状腺腺瘤及结节性甲状腺肿)以及20例取自甲状腺良性病变旁的正常甲状腺组织中Fascin蛋白的表达水平差异,分析Fascin蛋白表达水平与患者性别、年龄、有无淋巴结转移等临床特征的关系。结果 Fascin蛋白在甲状腺乳头状癌中的表达率(71.67%)明显高于良性甲状腺病变组及正常甲状腺组织组,三者之间比较差异有显著统计学意义(P＜0.01);甲状腺良性病变患者的甲状腺组织与正常甲状腺组织相比较,Fascin蛋白表达的阳性率均为零,差异无统计学意义(P＞0.05)。甲状腺乳头状癌伴淋巴结转移组中,Fascin蛋白的阳性表达率为91.30%,明显高于无淋巴结转移组(59.46%),两组之间比较差异具有统计学意义(P＜0.05)。结论 Fascin蛋白的表达与甲状腺乳头状癌的发生、发展及淋巴结转移密切相关,可以为甲状腺病变的良、恶性诊断,判断肿瘤的生物学行为及其预后提供理论依据,为临床治疗提供新的靶点。     

Overexpression of human tumor-associated antigen,RCAS1, is significantly linked to dedifferentiation of thyroid carcinoma

OBJECTIVE: Counterattack by RCAS1 on carcinoma to cytotoxic T cells and natural killer (NK) cells has been suggested as a contribution to carcinoma progression, because RCAS1 can inhibit their proliferation and induce apoptosis. In this study, we examined RCAS1 expression in various thyroid neoplasms in order to clarify its clinical significance. METHODS: We studied RCAS1 expression by means of immunohistochemistry using a mouse monoclonal antibody against RCAS1 for normal thyroid epithelium, follicular adenoma, follicular carcinoma, papillary carcinoma and undifferentiated (anaplastic) carcinoma. RESULTS: Normal epithelium and follicular adenoma did not express or only faintly expressed RCAS1. In thyroid carcinomas. RCAS1 overexpression was more frequently observed in anaplastic (undifferentiated) carcinomas than papillary (p < 0.0001) and follicular carcinomas (p = 0.0018). In follicular carcinoma, the widely invasive type more frequently overexpressed RCAS1 than the minimally invasive type (p = 0.0488). Furthermore, the incidences of RCAS1 overexpression increased with carcinoma dedifferentiation (p < 0.0001). CONCLUSION: These results suggest that RCAS1 may contribute to the progression of thyroid carcinoma with high biological aggressiveness.