子宫内膜癌患者血清uPA和PAI-1的含量变化及临床意义

目的:探讨子宫内膜癌患者血清尿激酶型纤溶酶原激活物(uPA)及纤溶酶原激活物抑制物-1(PAI-1)含量的变化及其临床意义。方法:用ELISA法测定35例子宫内膜癌(内膜癌组)、18例子宫内膜增生(内膜增生组)和16例正常子宫内膜患者(正常对照组)血清uPA和PAI-1含量及计算两者的比值。结果:内膜癌组患者血清uPA和PAI-1含量及uPA/PAI-1值均显著高于内膜增生组及正常对照组,差异有极显著性(P均<0.01)。内膜增生组及正常对照组,差异无统计学意义(P>0.05)。内膜癌组Ⅲ~Ⅳ期患者血清uPA和PAI-1含量与Ⅰ期相比差异有极显著性(P<0.01),Ⅲ~Ⅳ期患者血清uPA和PAI-1含量高于Ⅱ期(P<0.05),Ⅱ期患者血清uPA、PAI-1含量高于Ⅰ期(P<0.05)。内膜癌组患者血清uPA、PAI-1含量及uPA/PAI-1值随着手术病理分期及组织学分级的增高、肌层浸润深度的增加及淋巴结的转移而升高,差异有显著性(P均<0.05),而与患者病理类型无关(P>0.05)。结论:子宫内膜癌患者血清uPA和PAI-1含量及uPA/PAI-1值明显升高,并与其手术病理分期、浸润转移有关,提示其可能在内膜癌的发生、发展及浸润过程中起重要作用。     

RECK与MMP-9基因在子宫内膜癌中的表达及临床意义

目的:研究RECK和MMP-9在不同子宫内膜组织中的表达,探讨两者在子宫内膜癌的发生、发展和浸润转移中的作用。方法:应用链霉菌抗生物素蛋白-过氧化酶(SP)免疫组化法检测42例子宫内膜癌组织、15例子宫内膜不典型增生组织及26例正常增生期子宫内膜组织中RECK蛋白及MMP-9蛋白表达情况。结果:与正常增生期子宫内膜组织及子宫内膜不典型增生组织相比,子宫内膜癌组织中RECK蛋白阳性表达率显著降低(χ2=9.307,P<0.05),MMP-9蛋白阳性表达率显著增高(χ2=11.438,P<0.05),RECK蛋白与MMP-9蛋白在子宫内膜癌中的表达存在明显负相关(P<0.01)。RECK蛋白的表达水平与临床分期、组织学分级、肌层浸润深度及淋巴结转移密切相关(均P<0.05);MMP-9蛋白的表达水平与临床分期、组织学分级、肌层浸润深度密切相关(均P<0.05),而与淋巴结转移无关。结论:RECK蛋白的表达缺失和MMP-9的表达可能与子宫内膜癌的发生、发展及浸润转移有关。     

uPA系统在子宫内膜异位症中的表达及意义

目的:研究尿激酶型纤溶酶原激活剂(uPA)及其受体(uPAR)和纤溶酶原激活剂抑制剂(PAI-1)在子宫内膜异位症中的表达和意义。方法:采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接法(S-P法)分别检测30例子宫内膜异位症患者的异位内膜及其相应的在位内膜(研究组)以及30例正常子宫内膜(对照组)中uPA、uPAR、PAI-1的表达。结果:异位内膜和在位内膜及对照组子宫内膜组织中,uPA的表达分别为0.198、0.112、0.079;uPAR的表达分别为0.162、0.119、0.076;PAI-1的表达分别为0.230、0.158、0.080;异位内膜组织中uPA、uPAR、PAI-1与在位内膜及对照组相比,差异均有统计学意义(P<0.05,P<0.01);在位内膜组织中uPA、uPAR、PAI-1与对照组比较,差异亦有统计学意义(P<0.05)。无论是增殖期还是分泌期,异位内膜组织中uPA、uPAR、PAI-1的表达均高于在位内膜及对照组(P<0.05,P<0.01),在位内膜中uPA、uPAR、PAI-1的表达高于对照组(P<0.05)。结论:异位和在位子宫内膜组织中uPA、uPAR、PAI-1表达的变化可能与子宫内膜异位症的发生、发展有关。     

子宫内膜癌中Maspin的表达及其与雌激素受体表达的相关性研究

目的:检测Maspin蛋白在正常子宫内膜、不典型增生及内膜癌组织中的表达,及其与雌激素受体(ER)表达的关系,探讨Maspin在子宫内膜癌发生中的作用及其作用机制。方法:免疫组化SP法检测40例子宫内膜腺癌、18例不典型增生及10例正常子宫内膜(对照组)中Maspin蛋白的表达及其与子宫内膜癌患者临床病理特征和ER蛋白表达的关系。结果:Maspin阳性表达在正常子宫内膜组最高(9/10,90%),高于内膜不典型增生组(10/18,55.6%)和内膜癌组(17/40,42.5%),差异有统计学意义(P<0.05),在内膜癌中FIGOⅠ期的表达(13/20,65.0%)明显高于Ⅱ~Ⅲ期(4/20,20.0%;P<0.05),无淋巴结转移者(17/34,50.0%)明显高于有淋巴结转移者(0/6;P=0.030),但与组织学分级及肌层浸润程度无关(P>0.05)。ER在正常子宫内膜、内膜不典型增生及内膜癌组织的阳性表达率分别为(10/10,100.0%)、(13/18,72.2%)和(20/40,50.0%),各组间差异有统计学意义(P<0.05);内膜癌组织中FIGOⅠ期的表达(14/20,70.0%)明显高于Ⅱ~Ⅲ期(6/20,30.0%;P<0.05);内膜癌高、中、低分化组中ER表达率分别为(11/15,73.3%)、(8/18,44.4%)、(1/7,14.3%),组间差异有统计学意义(P<0.05);无淋巴结转移者(20/34,58.8%)明显高于有淋巴结转移者(0/6;P=0.020),肌层浸润≤1/2者(16/24,66.7%)明显高于肌层浸润>1/2者(4/16,25.0%;P<0.05)。子宫内膜癌中,Maspin的表达与ER的表达存在正相关关系(r=0.394,P<0.05)。结论:从正常子宫内膜、内膜不典型增生到内膜癌,Maspin蛋白表达逐渐降低,且其低表达与子宫内膜癌临床分期晚、淋巴结转移有关,并与ER蛋白表达呈一致性,提示Maspin蛋白的表达可能受雌激素调控,参与了子宫内膜癌发生发展和转移过程。     

HIF1α、Glut1在子宫内膜癌中的表达及其临床意义

目的:探讨HIF1α、G lut1在子宫内膜癌中的表达及其临床意义,并分析两者的相关性。方法:用免疫组化S-P法检测15例正常子宫内膜、17例不典型增生子宫内膜、45例子宫内膜癌组织中HIF1α、G lut1的表达。结果:HIF1α、G lut1在子宫内膜癌和不典型增生子宫内膜中的阳性率明显高于正常子宫内膜,差异有统计学意义(P<0.05)。在子宫内膜癌组织中HIF1α蛋白阳性表达率与组织病理学分级、手术病理分期无关(P>0.05),但与肌层浸润深度和淋巴结转移有关,差异有统计学意义(P<0.05);G lut1随病理组织学分级的增加、手术病理分期的进展、肌层浸润深度的加深和淋巴结转移,其阳性率逐渐上升,差异有统计学意义(P<0.05);HIF1α蛋白、G lut1蛋白表达呈正相关(r=0.741,P=0.000)。结论:HIF1α、G lut1蛋白的异常表达与子宫内膜癌的发生、发展有一定的关系。     

雌激素受体ERα36在子宫内膜癌组织中表达及临床意义的初步研究

目的:分析新型雌激素受体ERα36在子宫内膜癌组织中的表达与临床病理特征的关系。方法:免疫组织化学方法检测73例子宫内膜癌、20例正常子宫内膜、9例不典型增生子宫内膜组织切片ERα36的表达,并分析其与临床病理特征间的关系。结果:ERα36在子宫内膜癌组织中阳性表达率(32.9%,24/73)显著低于正常子宫内膜组织(85%,17/20)(P<0.01);ERα36阴性表达者较阳性表达者出现更多宫颈受侵(48.9%vs 20.8%,P<0.05);ERα36阳性表达者无疾病生存时间短于阴性表达者(P<0.01);ERα36表达与患者年龄、临床分期、组织学分级、肌层浸润、淋巴结转移和病理类型的差异无统计学意义(P>0.05);ERα36表达与ER、PR、PTEN、p53无显著相关性(P>0.05)。结论:ERα36在子宫内膜癌组织的表达明显低于正常子宫内膜组织;ERα36表达与ER无明显相关性,可能是子宫内膜癌预后的一个指标。     

子宫内膜癌标志物表达及其临床意义研究北大核心CSCD

目的探讨p53、磷酸酶与张力蛋白同源物(PTEN)、p16、人类表皮生长因子受体-2(HER-2)、Ki67的表达及其与子宫内膜癌发生发展的相关性。方法采用免疫组织化学法检测上海市普陀区妇婴保健院病理科2009月1年至2015年12月确诊的50例正常子宫内膜组织、20例不典型增生子宫内膜组织及75例子宫内膜癌中p53、PTEN、p16、HER-2及Ki67的表达,并对不同子宫内膜组织的表达结果进行比较。结果 p53、PTEN、p16、HER-2和Ki67在正常子宫内膜和子宫内膜癌中的表达差异均有统计学意义(P<0.05),在不典型增生子宫内膜中HER-2和Ki67表达显著高于正常子宫内膜(P<0.05),子宫内膜癌与不典型增生子宫内膜中PTEN、Ki67的表达差异有统计学意义(P<0.05)。在Ⅰ型和Ⅱ型子宫内膜癌之间p53、PTEN、p16、HER-2表达差异有统计学意义(P<0.05),Ki67在Ⅰ型和Ⅱ型子宫内膜癌间表达相近(P>0.05)。p53在子宫内膜癌的表达率与肿瘤的分化程度、浸润深度、脉管情况及临床分期密切相关(P<0.05),而PTEN、p16、HER-2和Ki67的表达与这些临床病理特征无关(P>0.05)。结论 p53、PTEN、p16、HER-2和Ki67蛋白的表达与子宫内膜癌的发生发展相关,在实际临床工作中可用于子宫内膜病变的病理诊断。     

雌激素受体、孕激素受体、C-erbB-2和Ki-67在子宫内膜癌中的表达及其与临床病理相关性

目的 探讨雌激素受体（ER）、孕激素受体（PR）、C-erbB-2和Ki-67在不同子宫内膜组织中的表达及其与临床病理的相关性。方法 采用免疫组化S-P法检测2004年1月至2013年1月郑州人民医院病理科存档30例正常子宫内膜、30例不典型增生、80例子宫内膜癌组织中ER、PR、C-erbB-2、Ki-67的表达。结果　ER、PR在正常子宫内膜、不典型增生和子宫内膜癌中表达逐渐降低(P<0.05),在不同分化子宫内膜癌组织类型中表达有差异(P<0.05);C-erbB-2在正常子宫内膜中不表达,在不典型增生中表达为53.33%和子宫内膜癌中表达为80.00%,两两比较差异有统计学意义(P<0.05);Ki-67在正常子宫内膜仅有少量表达,在不典型增生子宫内膜中表达为33.33%和子宫内膜癌中表达为63.75%,差异均有统计学意义(P<0.05)。C-erbB-2及Ki-67的表达与子宫内膜癌的分化程度、临床分期、肌层浸润深度及淋巴结转移4种病理特征均有关(P<0.05)。结论　ER、PR、C-erbB-2和Ki-67表达与子宫内膜癌的临床病理相关,可作为判断子宫内膜癌预后及指导临床治疗的指标。     

去整合素基质金属蛋白酶19在子宫内膜癌组织中的表达及意义

目的探讨去整合素基质金属蛋白酶19(ADAM19)与子宫内膜癌的发生、发展、浸润及转移的关系。方法选择2002年2月至2010年8月在广西医科大学第一附属医院妇科行手术治疗的患者共81例为研究对象,采用免疫组织化学的检测方法测定50例子宫内膜癌组织,16例不典型增生子宫内膜组织以及15例正常增殖期子宫内膜组织中ADAM19的表达情况,并分析其表达与各种临床参数的关系。结果 ADAM19蛋白在正常子宫内膜组织、不典型增生子宫内膜组织和子宫内膜癌组织中的高表达率分别为26.7%、75.0%和64.0%。在子宫内膜癌组织中的ADAM19的表达明显高于正常子宫内膜,差异有统计学意义(P<0.05)。ADAM19的表达与子宫内膜癌的组织学分级、肌层浸润深度、患者是否绝经有关(P<0.05),与子宫内膜癌的临床分期、淋巴结转移无关(P>0.05)。结论 ADAM19与子宫内膜癌的发生发展相关。     

子宫内膜癌中基质金属蛋白酶-9表达及其临床意义

目的研究基质金属蛋白酶(MMPs)-9在子宫内膜癌中的表达以及临床意义。方法对广州医学院第三附属医院1992-1997年收治的128例子宫内膜癌、30例不典型增生内膜及30例正常子宫内膜石蜡标本,应用免疫组织化学方法检测MMP-9蛋白表达情况。结果子宫内膜癌组织与子宫内膜不典型增生、正常子宫内膜组织相比,MMP-9蛋白的阳性表达率增加,差异有统计学意义(χ2=8.154,P<0.05)。MMP-9蛋白阳性表达与子宫内膜癌病理分级及淋巴转移有关(P<0.05)。结论 MMP-9蛋白在子宫内膜癌的浸润转移中起促进作用,可能与子宫内膜癌的预后不良有关。     

卵巢恶性肿瘤组织中u-PA、t-PA mRNA的表达

目的 :检测尿激酶型纤溶酶原激活剂 (u PA)和组织型纤溶酶原激活剂 (t PA)两因子的mRNA在卵巢肿瘤组织中的表达水平 ,初步探讨肿瘤细胞纤溶活性的变化与相关基因间的联系。方法 :采用实时监测荧光定量RT PCR技术 ,检测并比较卵巢恶性肿瘤组织和良性囊肿组织 (卵巢巧克力囊肿 )中u PA及t PA基因的表达。结果 :u PAmRNA在恶性肿瘤组织中的表达较良性卵巢囊肿组织中的表达显著升高 (P <0 .0 5 )。良性囊肿组织所表达的t PAmRNA较恶性组织显著升高 (P <0 .0 5 )。在高、中、低 3种分化程度的恶性肿瘤中 ,u PAmRNA拷贝数随肿瘤分化程度的降低而增加 (P <0 .0 5 ) ,t PAmRNA拷贝数随其分化程度的降低而降低 (P <0 .0 5 )。结论 :恶性肿瘤组织的u PA基因在转录水平上调 ,可能与卵巢肿瘤的恶性进展相关。t PA基因在转录水平下调 ,t PA在mRNA水平的高表达可能是组织分化较好的特征。     

Plasminogen activators in endometrial adenocarcinoma

Abstract. Gleeson N, Gonsalves R, McGuinness E, Bonnar J. Plasminogen activators in endometrial adenocarcinoma. Int J Gynecol Cancer 1991; 1: 223–226.
There are two disinct types of plasminogen activator, tissue type (t-PA) and urokinase (u-PA). We measured t-PA and u-PA antigen levels in extracts of 14 endometrial adenocarcinoma and of seven normal postmenopausal endometria. The concentration of endometrial t-PA was higher in normal than in malignant uteri ( p <0.05). In endometrial carcinoma t-PA levels were higher in less invasive disease. Endometrial u-PA levels were very low or absent in normal postmenopausal uteri and significantly higher ( p < 0.001) in malignant cases. An increase in u-PA and a decrease in t-PA are features of malignant transformation of the endometrium.     

On receptors for estrogens (E2) and androgens (DHT) in human endometrial carcinoma and ovarian tumours

Some human endometrial carcinomas contain receptors for estrogen (E2) and dihydrotestosterone (DHT). Analysis of 50 primary endometrial carcinomas by agar gel electrophoresis revealed a varying receptor pattern, absence of both receptors, sole presence of E2- or DHT- receptor, or presence of both. Highly differentiated tumours often had receptors of both types (7/18) and poorly differentiated tumours most often lacked them (1/10). Primary tumours with metastases (Stages III-IV) seldom had combined receptors, only in 2 cases out of 9. Growth of the tumour down in the cervical canal (Stage II) implied absence of combined receptors in all of the 13 cases studied. In 8 different ovarian tumours, presence of either E2- or DHT-receptors was found in 6. The findings are discussed in relation to hormonal treatment of the disease.     

Expression of the cell-cycle regulatory proteins (cyclins D1 and E) in endometrial carcinomas: correlations with hormone receptor status, proliferating indices, tumor suppressor gene products (p53, pRb), and clinicopathological parameters

PURPOSE OF INVESTIGATION: This study aimed to investigate the immunohistochemical expression of cyclins D1 and E in normal, hyperplastic and neoplastic endometrium, and their correlation with proliferative activity and clinicopathological features. METHODS: We carried out immunohistochemical techniques on archived material of formalin-fixed paraffin-embedded tissues using the antibodies against the cyclins D1 and E, PR-ER, p53, Ki67 (MIB1) and pRb with the streptavidin-biotin-peroxidase method in a total of 20 cases of normal endometrium, 32 cases of hyperplastic endometrium and 66 cases of endometrial carcinomas. RESULTS: Cyclin D1 and E immunoreactivity was observed in the nuclei of tumour cells in 18.2% and 39.1%, respectively, of the cases of endometrial carcinomas. Cyclin D1 labelling index was not significantly correlated with any of the clinicopathologic parameters examined. However, there was a significant correlation between the cyclin E labelling index and histological grade of carcinoma (p = 0.00096), which increased significantly with histological grades of malignancy. We also detected a significant correlation between cyclin E and PCNA (p < 0.0001) as well as with the tumor suppressor genes p53 and pRb (p = 0.052 and 0.0002, respectively) in endometrioid endometrial carcinoma. CONCLUSION: Our results indicate that cyclin E overexpression may be involved in the development and/or proliferation and differentiation of human endometrioid endometrial carcinoma. Immunoexpression of cyclin D1 does not appear to be associated with cell-cycle progression in the benign or malignant endometrium.     

Upregulation of bikunin in tumor-infiltrating macrophages as a factor of favorable prognosis in ovarian cancer

OBJECTIVE: This study was carried out to clarify the localization of bikunin, a Kunitz-type protease inhibitor, and relation between expression of individual bikunin protein and ovarian cancer progression. METHODS: We performed a retrospective study on the immunohistochemical expression of bikunin, urokinase-type plasminogen activator (uPA) and macrophages (CD68) in surgical specimens derived from 89 ovarian cancer patients to investigate correlations between the expression of bikunin and the clinicopathologic features and the prognosis. Furthermore, bikunin and uPA levels were measured by immunoblot analysis. RESULTS: Immunohistochemical staining revealed that the localization of bikunin was similar to that of CD68 for macrophages. We identified high expression of bikunin in 40 (45%) of 89 ovarian cancers. The results of Western blot analysis showed a significant correlation with immunohistochemical data. There was a significant inverse correlation between bikunin levels and uPA levels in ovarian cancer tissues. High bikunin expression was an independent predictor for disease-free survival (P = 0.040) and overall survival (P = 0.042). The 5-year survival rate of the 49 patients with low bikunin expression in ovarian cancers was 39%, whereas that of the other 40 patients with high bikunin expression was 63%. In addition, macrophage-derived bikunin protein was induced by exogenous IL-6. CONCLUSION: Bikunin derived from tumor-infiltrating macrophages might be a prognostic indicator as an antiinvasive factor supplied from macrophages within and around the tumor possibly through down-regulation of tumor-associated uPA expression.     

Synchronous ovarian and endometrial carcinoma: a strong link to endometriosis?

PURPOSE: To further study the clinicopathological features of synchronous ovarian and endometrial carcinomas. METHODS: We retrospectively studied all cases of synchronous ovarian and endometrial carcinomas diagnosed in our laboratory over the last 15-year period. The pathological findings were correlated with the clinical records of the patients. RESULTS: Seven cases of synchronous primary ovarian and endometrial carcinomas were retrieved. The most common presenting symptom was abnormal vaginal bleeding (5 cases, 71.4%). Five patients (71.4%) were postmenopausal and two (28.6%) were nulliparous. All seven patients had Stage I ovarian and endometrial carcinomas of endometrioid histology. Moreover, in all seven ovarian carcinomas endometriosis foci were observed, while atypical endometriosis was found in four of them. With the exception of one patient, who received adjuvant postoperative radiation, all remaining patients were treated with surgery alone. All patients were alive and free of disease at completion of the study. CONCLUSION: The correct classification of synchronous primary ovarian and endometrial carcinomas is often problematic because of the frequent confusion with their metastatic counterparts. Although the exact etiology remains unclear, endometriosis seems to be a major risk factor for their development.     

乌司他丁通过调节uPA表达对绒癌细胞体外侵袭能力的影响

目的:探讨尿胰蛋白酶抑制剂(UTI)乌司他丁(Ulinastatin)对绒癌细胞侵袭力的影响及其作用机制。方法:Matrigel体外侵袭实验比较绒癌细胞JEG-3和JAR的体外侵袭能力及不同浓度乌司他丁对JEG-3细胞体外侵袭能力的影响,半定量RT-PCR法检测两种细胞内uPA mRNA表达及不同浓度乌司他丁对JEG-3细胞中uPA mRNA表达的影响。结果:JEG-3细胞体外侵袭能力(201±21)明显强于JAR细胞(106±18),两者差异有统计学意义(P0.001);细胞内uPA mRNA表达JEG-3(0.3835±0.01255)明显高于JAR(0.1057±0.01664),两者差异有统计学意义(P0.01);在本实验的浓度范围内,乌司他丁浓度达100U/ml及以上时,各组JEG-3细胞中uPA mRNA表达水平、穿膜细胞数与对照组相比,差异均有统计学意义(P0.05),不同浓度组间差异亦有统计学意义(P0.05),uPA mRNA表达水平、穿膜细胞数与药物浓度之间呈负相关(r=-0.862,P0.05;r=-0.885,P0.05);细胞侵袭力与细胞中uPA mRNA表达水平呈正相关(r=0.996,P0.05)。结论:uPA可能是与绒癌侵袭转移相关的基因,UTI可通过下调uPAmRNA表达抑制绒癌JEG-3细胞的体外侵袭转移。     

Bax,Bcl-2, and p53 expression in endometrial cancer

BACKGROUND: It has not been fully clarified whether alteration of Bax and other apoptosis-relating proteins of Bcl-2 and p53 is involved in endometrial carcinogenesis. METHODS: A total of 56 frozen tissues, which included 14 normal endometria, 13 endometrial hyperplasias (10 without atypia and 3 with atypia), and 29 endometrial carcinomas, were examined for the expression of Bax, Bcl-2, and p53 using immunohistochemistry. For Bax-negative cases, PCR-direct sequencing was performed for the bax gene. For cases with p53 overexpression, mutational analysis was performed for the p53 gene using a yeast functional assay and sequencing. RESULTS: Both Bax and Bcl-2 were distinctly expressed in the normal proliferative phase endometrium. A decreased Bcl-2/Bax ratio in the secretory phase endometrial gland cells due to suppressed Bcl-2 expression was observed. Bax expression was positive in all 13 endometrial hyperplasias, while it was absent in 6 of 29 endometrial carcinomas (20.7%). Negative Bax expression in endometrial carcinoma was not related to tumor stage, histologic subtype, or other histopathologic prognostic factors. Bax expression showed no relationship to either p53 overexpression or Bcl-2 expression. In the DNA of 6 Bax-negative cases, we found a frameshift insertion mutation at codon 58 (AAG to CAAG) in the BH3 domain despite the absence of mutation in the (G)8 tract, suggesting that this codon may be another preferred target for bax mutation other than the (G)8 tract. Mutational analysis was available for 7 of 10 cases with p53 overexpression, in which 5 cases were found to have a missense mutation and 2 cases had no mutation of the p53 gene. At least 10 of 29 (34.5%) cases of endometrial carcinoma were associated with sequence-verified mutation in the bax gene and/or p53 gene. CONCLUSIONS: The bax gene frameshift mutation appears to cause a loss of Bax expression in endometrial carcinoma. Codon 58 may be a preferred target of bax gene mutation in endometrial carcinomas. The bax gene mutation seems to occur in the early stage of the genesis of a subset of endometrial carcinomas.