甲状腺乳头状癌患者血清SIL-2R测定与肿瘤组织ER受体表达

目的:研究可溶性白介素受体(sol-uble interleukin- 2 receptor, SIL- 2R)及雌激素受体(estrogen receptor, ER)在甲状腺乳头状癌的表达。方法: 应用 ELISA双抗夹心法和免疫组化 SP法对 50 例甲状腺乳头状癌、20 例滤泡状癌及 10 例髓样癌进行SIL- 2R及 ER测定。结果: 甲状腺癌患者术前血清中 SIL -2R含量(118. 20±43 50)pmol/L,明显高于甲状腺结节组(50 .28±12. 28) pmol/L 及对照组(49. 25±13. 32)pmol/L;术后20- d基本降至正常;甲状腺癌血清中SIL-2R升高与甲状腺癌的病理类型无明显关系;甲状腺乳头状癌 ER阳性表达率(67 3%)显著高于滤泡状癌(40 0%)及正常组织 ( 8 0%); 原发癌 ER 阳性率(74. 2%)明显高于复发癌(20 .0%);无淋巴结转移的甲状腺乳头状癌 ER 阳性率(68. 5%)高于有颈部淋巴结转移的甲状腺乳头状癌(46 .6%)。结论:SIL- 2R和 ER对判断甲状腺良、恶性疾病和评价疗效及预后有一定临床意义。     

子宫颈癌患者尿激酶型纤溶酶原激活物和抑制物的表达及其临床意义的研究

目的 :研究纤溶酶原激活物和抑制物在子宫颈癌的发生、发展及侵袭转移过程中的规律及对临床的指导意义。方法 :采用ELISA法检测 4 2例子宫颈癌患者和 10例良性子宫肿瘤患者的血浆和组织中uPA和PAI 1含量 ,按良恶性、手术前后、临床分期和组织类型等分别进行对照分析。结果 :子宫颈癌患者血浆中uPA和PAI 1含量随临床分期的升高逐渐增加。宫颈癌患者血浆uPA和PAI 1含量术后显著降低。淋巴结转移组血浆uPA含量高于无转移组。癌组织中的uPA和PAI 1含量高于癌周组织。正常宫颈、宫颈上皮内瘤变、宫颈鳞癌组织uPA含量呈上升趋势。腺癌的组织uPA含量高于鳞状细胞癌组 ,PAI 1含量无差异。结论 :检测宫颈癌患者uPA和PAI 1含量可能对其侵犯范围、盆腔淋巴结转移情况、预后等有一定的参考价值     

L1CAM在甲状腺乳头状癌组织及细胞中的表达及与临床病理特征的关系

目的:检测甲状腺乳头状癌组织及细胞株中L1CAM表达,探讨其与临床病理特征的相关性及意义。方法:选取手术切除甲状腺乳头状癌组织、对应的癌旁组织及正常甲状腺组织标本各32例,甲状腺癌细胞株及正常甲状腺细胞株。采用Western blot及qRT-PCR检测组织及细胞株中L1CAM的表达,观察其与肿瘤部位、直径、数目、分化程度、淋巴结转移及AJCC分期等临床病理参数的关系。结果:L1CAM蛋白及mRNA在甲状腺乳头状癌组织中表达高于癌旁甲状腺组织,在正常甲状腺组织无表达（P<0.05）;甲状腺乳头状癌组织中L1CAM蛋白水平与肿瘤直径、肿瘤数目、淋巴结转移、AJCC分期具有相关性（P均＜0.05）,肿瘤直径大于1 cm、肿瘤多发、淋巴结转移及AJCC分期Ⅲ-Ⅳ的甲状腺癌组织中L1CAM表达量高;L1CAM蛋白及mRNA在BHT101、B-CPAP甲状腺癌细胞株中均有表达,在正常甲状腺上皮细胞NTHY-ORI 3-1无表达,在BHT101中高于其他细胞株（P<0.05）。结论:L1CAM在甲状腺乳头状癌组织及细胞中表达上调,与甲状腺乳头状癌发展及转移恶性临床病理特征相关。     

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。     

存活素和CD44V6在甲状腺癌组织中的表达及意义

目的探讨细胞凋亡抑制因子存活素（survivin）和黏附分子CD44V6在甲状腺癌中的表达及其与甲状腺癌侵袭转移的关系。方法采用S-P免疫组织化学染色法，检测100例甲状腺癌和10例正常甲状腺组织中Survivin、CD44V6表达情况。结果Survivin在正常甲状腺组织中无表达，在70例甲状腺乳头状癌（PTC）及30例甲状腺滤泡癌（FTC）中阳性表达率分别为45．7％（32／70）、53．3％（16／30）；CD44V6在70例甲状腺乳头状癌及30例甲状腺滤泡癌中阳性表达率分别为50．0％（35／70）、66．7％（20／30），显著高于正常甲状腺组织；在甲状腺癌组织中Survivin表达与CD44V6表达具有显著相关性（7=0．386，P〈0．05），且两者表达与甲状腺癌的临床分期及有、无淋巴结转移显著相关。结论Survivin和CD44V6表达与甲状腺癌侵袭转移密切相关，且呈协同效应。     

血型抗原Lewis A和Lewis X在甲状腺乳头状癌中的表达

目的 :探讨血型抗原LewisA和LewisX在甲状腺乳头状癌中表达的意义。方法 :采用免疫组织化学EnVision方法 ,测定血型抗原LewisA和LewisX在 70例甲状腺乳头状癌和 70例癌旁正常甲状腺滤泡上皮 ,以及 16例甲状腺滤泡性腺瘤、17例结节性甲状腺肿和 14例桥本氏甲状腺炎中的表达。结果 :LewisA和LewisX在甲状腺乳头状癌中的表达阳性率分别为 94 3% ( 66/ 70 )和 85 7% ( 60 / 70 ) ,癌旁正常甲状腺滤泡上皮中的表达阳性率分别为 2 9% ( 2 / 70 )和 5 7% ( 4 / 70 )。肿瘤直径≥ 1cm组LewisX的表达强度较肿瘤直径 <1cm组明显增高 ,P <0 0 1。淋巴结转移组LewisX的表达强度较非转移组显著增高 ,P <0 0 1。结论 :LewisA和LewisX可作为诊断甲状腺乳头状癌的参考指标。LewisX的表达强度与肿瘤浸润及转移有关     

甲状腺癌的诊断和治疗

甲状腺癌(简称甲癌)其病程长,生物学特性差异较大,影响预后因素多,所以在诊断技术、治疗方式和疗效等方面意见不一。 发病率、病理分类和分期 甲癌发病率约占全部癌瘤的1％。据病理形态和生物学特性分为四型:乳头状癌(隐匿型、甲状腺内型和外型);滤泡状癌(非侵袭性和侵袭性型);髓样癌;未分化癌(巨细胞和小细胞型)。其发病率分别为62.3％,17.6％,6.5％,13.6％。病理分期:Ⅰ期,乳头状癌(隐性癌、甲状腺内型)、非侵袭性滤泡癌、髓样癌(无淋巴结转移;Ⅱ期,乳头状癌(甲状腺外型);Ⅲ期,侵袭性滤泡癌,髓样癌(伴淋巴结转移);Ⅳ期,未分化癌,其10年生存率分别为90％,60—90％,10—60％,<10％。临床分期:Ⅰ期,限于甲状腺;Ⅱ期,区域淋巴结受累;Ⅲ期,侵犯邻近器官;Ⅳ期,伴远处转移。     

S100A6蛋白在甲状腺癌中的表达及意义

[目的]探讨S100A6蛋白在甲状腺癌中的表达及临床意义。[方法]应用免疫组织化学法检测108例甲状腺石蜡标本中S100A6蛋白表达情况,其中甲状腺癌57例(乳头状癌43例,滤泡状癌14例),甲状腺滤泡型腺瘤15例,癌旁甲状腺组织36例。[结果]S100A6蛋白在甲状腺癌、甲状腺滤泡型腺瘤及癌旁正常甲状腺组织中的阳性表达率分别为82.5%(47/57)、40.0%(6/15)和16.7%(6/36),三组比较差异有统计学意义(P<0.01)。乳头状癌、滤泡状癌中S100A6蛋白的阳性表达率分别为97.7%(42/43)、35.7%(5/14),乳头状癌组织中S100A6蛋白的阳性表达率显著高于滤泡状癌(P<0.01)。[结论]S100A6蛋白在甲状腺癌组织中过表达,不同病理类型甲状腺癌组织S100A6蛋白表达水平不同。S100A6有望成为甲状腺癌的早期诊断和鉴别诊断标志物之一。     

甲状腺肿瘤端粒酶逆转录酶mRNA的表达

目的　探讨端粒酶活性在甲状腺肿瘤中的诊断价值。方法　用核酸原位杂交检测了 2 0例甲状腺乳头状癌 ,2 0例甲状腺滤泡状癌 ,9例甲状腺腺瘤端粒酶逆转录酶 (TERT)亚基的mRNA。结果　 2 0例甲状腺乳头状癌阳性检出率为 90 % ,2 0例甲状腺滤泡状癌阳性检出率为 85 % ,明显高于 9例甲状腺腺瘤的阳性检出率 (11.1% ,P <0 .0 1)。结论　端粒酶活化在甲状腺癌的发生过程中起重要作用 ,端粒酶可以作为一种有效的恶性肿瘤标记物用于甲状腺癌的诊断。     

MMP-9及TIMP-1 mRNA在甲状腺肿瘤中的表达及临床意义

目的研究MMP-9及TIMP-1 mRNA在不同类型甲状腺肿瘤组织及不同临床病理特征甲状腺乳头状癌(PTC)中的表达,探讨其在甲状腺癌浸润、转移中的作用.方法采用石蜡切片、原位杂交法检测了20例甲状腺乳头状癌,20例甲状腺腺瘤,20例结节性甲状腺肿和20例癌旁正常甲状腺组织中MMP-9、TIMP-1 mRNA的表达.结果与癌旁正常甲状腺比较各类型肿瘤组织中MMP-9 mRNA杂交信号均呈增强的趋势(P＜0.01),与甲状腺癌比较,结节性甲状腺肿和甲状腺腺瘤组织中MMP-9 mRNA杂交信号均呈减弱的趋势(P＜0.05);同时,MMP-9 mRNA在甲状腺癌中的表达与肿瘤的大小、临床分期、淋巴结转移、预后指数呈正性调节关系(MMP-9 mRNA表达高者恶性度高、预后差,P＜0.05或P＜0.01).TIMP-1 mRNA在癌旁正常甲状腺组织、良性甲状腺结节及甲状腺癌中均有不同程度的表达,与癌旁正常甲状腺组织比较各类型肿瘤组织中TIMP-1 mRNA表达均呈增加的趋势,但只有甲状腺癌组明显高于正常甲状腺组,差异有显著(P＜0.05);与甲状腺癌比较,结节性甲状腺肿和甲状腺腺瘤组织中TIMP-1 mRNA表达没有明显改变(P＞0.05);同时TIMP-1 mRNA在甲状腺癌中的表达与临床病理特征呈负性调节关系(TIMP-1mRNA表达低者恶性度高、预后差,P＜0.05或P＜0.01).结论MMP-9及TIMP-1 mRNA的表达与甲状腺癌的浸润、转移密切相关,MMP-9及TIMP-1 mRNA表达有望成为判断甲状腺乳头状癌浸润、转移和预后较可靠的指标.     

喉癌组织中尿激酶型纤溶酶原激活剂及其抑制剂的表达及意义

目的:研究尿激酶型纤溶酶原激活剂(urokinasetypeplasminogenactivator,uPA)和纤溶酶原激活剂抑制剂1(plasminogenactivatorinhibitor1,PAI1)在喉癌组织中的表达及其临床意义。方法:应用SABC法检测51例声门上型喉癌患者中的uPA与PAI1的表达,结合临床随访,分析其与临床病理指标的关系及预后的作用。结果:uPA和PAI1的染色阳性率分别为64.7%(33/51)和70.6%(36/51)。uPA和PAI1的表达均与临床分期和颈淋巴结状况相关,与肿瘤大小、T分期和病理学分级无关。单因素分析显示,uPA和PAI1的表达与颈淋巴结转移有相似预后作用;多因素分析显示,uPA和颈淋巴结转移是影响患者预后的独立因子。结论:uPA和PAI1的表达与喉癌的临床分期和颈淋巴结转移有关,uPA阳性表达者可能预后较差。     

Expression of urokinase plasminogen activator, its receptor and type-1 inhibitor in malignant and benign prostate tissue

The plasminogen activation (PA) cascade participates in degradation of extracellular matrix during cancer invasion. We have studied the expression of urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and immunoreactivity, and type-1 plasminogen activator inhibitor (PAI-1) mRNA and immunoreactivity in 16 prostate adenocarcinomas and 9 benign prostate hyperplasias. uPA mRNA and uPAR mRNA expression were found in 9 and 8 of the adenocarcinomas, respectively, and in 7 and 6 of the benign hyperplasias, respectively. In both malignant and benign lesions, expression of these 2 mRNAs was predominantly seen in cells identified as macrophages, which in most of the carcinomas (approximately 90%) were located in the interstitial tissue between the tumor cell islands, while in most of the benign hyperplasias they were located in the lumen of the glands and were in only a few cases (approximately 30%) found in the interstitial tissue. uPAR immunoreactivity correlated with the mRNA expression and was, in addition, found in neutrophils. PAI-1 mRNA was detected in 13 of the 16 carcinomas and in 8 of the 9 benign hyperplasias, located in scattered fibroblast-like cells in both groups, in some vascular structures and in a few macrophages located in the interstitial tissue of both malignant and benign lesions. A similar expression pattern was found for PAI-1 immunoreactivity. In 8 of the 16 carcinomas, all 3 components were present, and in several areas colocalization was observed in stromal cells in close proximity to cancer cell islands. No immunoreactivity and/or mRNA expression of uPA, uPAR or PAI-1 was observed in cancer cells or in other epithelial cells in any of the cases.     

Differential expression of the components of the plasminogen activating system in human thyroid tumour derived cell lines and papillary carcinomas

We characterised the expression of the plasminogen activators (uPA and tPA), the uPA receptor (uPAR) and the PAs inhibitors (PAI-1 and PAI-2) in human thyroid cell lines derived from normal thyroid, follicular adenoma, follicular, papillary and anaplastic carcinomas. Urokinase PA activity was detected in the supernatant of normal thyrocytes and augmented in those of all tumour cells. Quantitative RT-PCR analysis showed that uPA, uPAR and PAI-1 mRNAs increased in all carcinoma cells. Similar results were found in 13 papillary thyroid carcinoma (PTC) tissues which were mirrored in Western blot experiments. A correlation was found between tumour size and uPA mRNA increase, and higher levels of uPA and uPAR mRNAs were found in metastatic PTC. In conclusion, thyroid carcinoma cell lines and PTC overexpress uPA, uPAR and PAI-1 and the correlation of uPA and its cognate receptor with tumour size and metastasis may suggest their potential prognostic relevance in thyroid cancer.     

The urokinase-type plasminogen activator system in resected non-small-cell lung cancer

Background:Urokinase-type plasminogen activator (uPA), itsreceptor (uPAR) and plasminogen activator inhibitors (PAI-1 and PAI-2), allplay important roles in tumour invasion and metastasis. The tumour levels ofthe components of the urokinase-type plasminogen activator system (uPA-system)may help to identify individuals with a poor prognosis in postoperativenon-small-cell lung cancer (NSCLC) patients. Patients and methods:The levels of uPA, uPAR PAI-1 and PAI-2 weremeasured by enzyme-linked immunosorbent assay (ELISA) in triton-extracts,prepared from 88 NSCLC tissues (stage I–IIIa) and 74 normal lung tissuesfrom the same patients. Results:The expression levels of uPA, uPAR, PAI-1 and PAI-2 weresignificantly higher in tumour tissues as compared to their normal equivalents(all, P < 0.0001). Significant relations were found between genderand uPA (P = 0.04) or uPAR (P < 0.001), and between PAI-2and pathological stage (P = 0.03). For none of the studied factorsof the uPA-system a significant relation with survival was found, neither inall patients, nor in the subgroups of patients with squamous-cell lungcarcinoma or adenocarcinoma. Conclusions:The expression levels of the components of theuPA-system were higher in NSCLC tissue as compared to normal lung tissue, butthere were no significant relationships between their levels and survival.     

Plasminogen activator inhibitor type 2 in breast cancer.

The serine protease urokinase plasminogen activator (uPA) is causally involved in cancer invasion and metastasis. Activity of this protease in vivo is controlled principally by two inhibitors, one of which is plasminogen activator inhibitor type 2 (PAI-2). In this study, we show that PAI-2 levels were significantly higher in primary breast carcinomas (n = 152) than benign breast tumours (n = 18). In the primary cancers, PAI-2 levels correlated weakly but significantly with those of uPA and PAI-1, but not with tissue type plasminogen activator (tPA) or uPA receptor (uPAR) levels. Using Northern blotting, mRNA for PAI-2 was found in 28.6% of 49 primary breast cancers. In contrast to findings at the protein level, PAI-2 mRNA levels failed to correlate with those for uPA or PAI-1. After immunocytochemistry with primary cancers, PAI-2 was detected predominantly in the malignant cells of primary carcinomas but was also present in stromal cells. Using the median value as a cut-off point, PAI-2 showed no significant relationship with either disease-free interval or overall survival. However, using an optimum cut-off value, patients with low levels of PAI-2 had a worse outcome than those with a high level. We conclude that, unlike PAI-1, high levels of PAI-2 may be a favourable prognostic marker in breast cancer.     

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer - correlation with traditional prognostic factors

Background

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients.

Patients and methods.

606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman’s rank correlation, Mann Whitney U test and χ² test for statistical analysis.

Results

Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002).

Conclusions

Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated.     

Clinical utility of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 determination in primary breast cancer tissue for individualized therapy concepts

Invasion factors urokinase-type plasminogen activator (uPA) and its plasminogen activator inhibitor (PAI-1) are the only novel tumor biological prognostic factors validated at the highest level of evidence with regard to their clinical utility in breast cancer. Antigen levels of both factors present in extracts of primary tumor tissue are determined by standardized, quality-assured enzyme-linked immunosorbent assays. Numerous studies showed that patients with low levels of uPA and PAI-1 have a significantly better survival than patients with high levels of either factor. Recently, these data have been validated by a European Organization for Research and Treatment of Cancer pooled analysis comprising more than 8000 breast cancer patients. The particular combination of both factors, uPA/PAI-1 (both low vs. either or both factors high), outperforms the single factors as well as other traditional prognostic factors with regard to risk group assessment, particularly in node-negative breast cancer. Node-negative breast cancer patients with low levels of uPA and PAI-1 have a very good prognosis and, as such, may be candidates for being spared the burden of adjuvant chemotherapy. In contrast, node-negative patients with high uPA/PAI-1 are at a substantially increased risk of relapse, comparable to that of patients with > or = 3 involved axillary lymph nodes. First results from a multicenter prospective randomized therapy trial in node-negative breast cancer (Chemo N(0)) as well as recent retrospective analyses indicate that these high-risk patients benefit from adjuvant chemotherapy. Thus, combined determination of the invasion factors uPA and PAI-1 supports risk-adapted individualized therapeutic strategies in patients with primary breast cancer, particularly in those with node-negative breast cancer.     

Evaluate the expression of uPA, PAI-1 in human gastric cancer and its correlation with the angiogenesis by the application of tissue microarray

OBJECTIVE To investigate the expression of urokinase-type plasminogen （uPA）, its inhibitor-1 （PAI-1） mRNA and its protein in human gastric cancer and to find out the relationship among the tumor differentiation, angiogenesis, and other clinical pathologic factors. METHODS In situ hybridization （ISH） was used to get the uPA, PAI-lmRNA in 110 cases with human gastric cancer in 2-tissue microarray （TMA）. Immunohistochemical staining （S-P method） for uPA, PAI-1 protein and CD34 were performed in the 110 cases in 2 TMA. RESULTS The expression of the uPA, PAI-lmRNA and their protein happened in the cytoplasm of gastric cancer cells were induced by the poor differentiation of the GC, and the expression of uPA had an increasing trend while the expression of the PAI-1 had a decreasing trend. The microvessel density （MVD） had a positive correlation with the clinical stages and the significant relationship with the lymph node metastasis （P 〈 0.05）. The MVD in uPA positive group was significantly higher than those in uPA negative group （P 〈 0.05）. The expression of PAI-1 has no correlation neither with the clinical stages nor the lymph node metastasis. CONCLUSION The uPA play an important role in invasion and metastasis of GC through promoting angiogenesis. Interdicting the secretion and function of the uPA may allow the target therapy against the tumor invasion. As a new high-throughput technology, the tissue microarray is a valuable way to be used in clinical treatment.     

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer.

The uPA-mediated pathway of plasminogen activation is central to cancer metastasis. Whether uPA and PAI-1 are related to local recurrence, metastatic spread or both is not clear. We present a retrospective study of 429 primary breast cancer patients with a median follow-up of 5.1 years, in which the levels of uPA and PAI-1 in tumour extracts were analysed by means of an enzyme-linked immunosorbent assay. The median values of uPA and PAI-1, which were used as cut-off points, were 4.5 and 11.1 ng mg(-1) protein respectively. The levels of uPA and PAI-1 were correlated with tumour size, degree of anaplasia, steroid receptor status and number of positive nodes. Patients with high content of either uPA or PAI-1 had increased risk of relapse and death. We demonstrated an independent ability of PAI-1 to predict distant metastasis (relative risk 1.7, confidence limits 1.22 and 2.46) and that neither uPA nor PAI-1 provided any information regarding local recurrence.