E-钙粘素和β-连环素对葡萄胎恶变预测的价值

目的 :探讨E 钙粘素和 β 连环素的表达在葡萄胎恶变预测中的价值。 方法 :采用免疫组化SP法检测 2 2例正常早孕绒毛和 35例葡萄胎石蜡包埋组织中E 钙粘素和β 连环素的表达 ,利用等级资料的秩和检验与Logistic回归法结合临床资料进行结果分析。结果 :E 钙粘素和β 连环素在正常早孕绒毛和葡萄胎组织中均有表达 ,在正常早孕绒毛组和葡萄胎非恶变组的表达强度差异无显著性 (P >0 .0 5 ) ;而在葡萄胎恶变组的表达强度明显低于正常绒毛和葡萄胎非恶变组 (P <0 .0 1)。葡萄胎恶变与E 钙粘素和 β 连环素的表达强度、血 β HCG值和卵巢黄素化囊肿有关 (P <0 .0 5 )。结论 :E 钙粘素和β 连环素对葡萄胎恶变预测有一定参考价值。     

上皮型钙粘附素在妊娠滋养细胞疾病中的表达及与滋养细胞肿瘤侵袭的关系

目的 :明确上皮型钙粘附素 (E cd)在妊娠滋养细胞疾病中的表达及其与恶性滋养细胞肿瘤侵袭的关系。方法 :应用免疫组织化学SP方法检测葡萄胎、侵蚀性葡萄胎及绒毛膜癌石蜡切片中E cd的表达情况 ,并分析其与恶性滋养细胞肿瘤侵袭的关系。结果 :①E cd在葡萄胎、侵蚀性葡萄胎及绒癌的细胞滋养细胞中表达存在差别 (P <0 .0 0 1)。②E cd在侵蚀性葡萄胎及绒毛膜癌中细胞滋养细胞上的表达与葡萄胎比较均明显下降 (P <0 .0 0 1)。③侵蚀性葡萄胎及绒癌浸润子宫肌层的深度与E cd的表达状况差异有显著性 (P <0 .0 5 )。结论 :E cd表达下降或缺失与恶性滋养细胞的高侵袭力密切相关。     

层粘蛋白及受体在正常妊娠及妊娠滋养细胞疾病中的表达

目的探讨层粘蛋白(LN)及其受体(LN-R)在正常妊娠及妊娠滋养细胞疾病中的表达及其与恶性滋养细胞肿瘤侵袭的关系。方法收集1991年1月至2003年12月温州医学院附属一院正常妊娠、葡萄胎、侵蚀性葡萄胎及绒毛膜癌(绒癌)石蜡包埋组织,应用免疫组织化学SP方法检测各组中LN、LN-R的表达情况。结果LN、LN-R在正常妊娠、葡萄胎、侵蚀性葡萄胎及绒癌中的表达差异有非常显著性意义(P<0·01)。LN、LN-R在侵蚀性葡萄胎及绒癌中的表达与正常妊娠、葡萄胎比较差异有非常显著性意义(P<0·01)。结论LN、LN-R在妊娠滋养细胞疾病中的表达异常与恶性滋养细胞的高侵袭力密切相关。     

妊娠滋养细胞疾病中EMT相关蛋白CK19和N-cad表达的研究

目的:探讨上皮细胞向间质转化(EMT)相关蛋白细胞角蛋白19(CK19)和神经钙黏蛋白(N-cad)在妊娠滋养细胞疾病发生、发展中的作用。方法:采用免疫组化SP法检测了41例正常早孕绒毛(NP)、31例葡萄胎(HM)、32例妊娠滋养细胞肿瘤(GTN)[26例侵蚀性葡萄胎(IM)+6例绒癌(CCA)]中CK19和N-cad的定位及表达情况。结果:NP组中CK19和N-cad蛋白相对表达均显著高于HM、GTN组(P0.05),HM组显著高于GTN组(P0.05)。CK19与N-cad的表达无相关性(r=0.202,P=0.268)。结论:伴随着滋养细胞恶性程度的升高,CK19和N-cad表达逐渐降低,提示EMT可能与滋养细胞的恶性转化有关。     

p16 Cyclin D1在妊娠滋养细胞疾病组织中的表达及意义

目的：探讨p16、 CyclinD1基因在滋养细胞肿瘤发生方面的意义。方法：用免疫组化SP法,对49例滋养细胞疾病组织（葡萄胎首次清宫标本32例,侵蚀性葡萄胎及绒癌子宫标本分别为12例和5例）和4例早孕正常绒毛组织中p16和CyclinD1进行检测。结果：在早孕绒毛组织中,p16和CyclinD1表达分别为全部阳性和全部阴性。在不恶变葡萄胎、以后发生恶变的葡萄胎和滋养细胞肿瘤中p16表达呈下降趋势,CyclinD1表达呈上升趋势。p16和CyclinD1表达阳性率在不恶变葡萄胎与以后发生恶变的葡萄胎组间、在不恶变葡萄胎组与侵蚀性葡萄胎间均有显著差异（P＜0.05);而以后发生恶变的葡萄胎与侵蚀性葡萄胎间及侵蚀性葡萄胎与绒毛膜癌间无显著差异（P＞0.05)。结论：p16表达缺失、CyclinD1过表达可能在滋养细胞恶性转化、侵蚀性葡萄胎发生中起重要作用。检测葡萄胎首次清宫标本p16及CyclinD1表达,可能在判断葡萄胎预后方面具有重要意义。     

血管生成素在妊娠滋养细胞疾病中表达的临床意义探讨

目的:通过检测血管生成素(ANG)在人正常早孕绒毛组织、葡萄胎及妊娠滋养细胞肿瘤中表达的差异性,探讨ANG在妊娠滋养细胞疾病(GTD)表达的意义。方法:采用免疫组化(En Vision)法检测人正常早孕绒毛组织28例、葡萄胎组织26例、妊娠滋养细胞肿瘤组织14例(其中侵蚀性葡萄胎1例、绒毛膜癌12例、胎盘部位滋养细胞肿瘤1例)中ANG蛋白的表达以及定位情况。结果:ANG蛋白在人正常早孕绒毛组织、葡萄胎及妊娠滋养细胞肿瘤组织中均有表达且主要定位于细胞质和细胞膜、少量表达于细胞核;ANG阳性表达率葡萄胎组(100.0%)高于正常早孕绒毛组(60.7%)(P0.05)和妊娠滋养细胞肿瘤组(85.7%)(P0.05),妊娠滋养细胞肿瘤组高于正常早孕绒毛组(P0.05)。在妊娠滋养细胞肿瘤中,ANG阳性表达率在年龄≥40岁组(83.3%)高于年龄40岁组(75.0%)(P0.05);临床分期晚期组(Ⅲ、Ⅳ期)(88.9%)高于早期组(Ⅰ期、Ⅱ期)(80.0%)(P0.05);FIGO预后评分高危组(87.5%)高于低危组(83.3%)(P0.05)。结论:ANG在GTD组织中的表达明显高于在正常早孕绒毛组织,且在妊娠滋养细胞肿瘤晚期、高危患者表达增高,表明ANG的过表达可能参与了GTD的发生过程。     

化学发光法测定绒毛膜促性腺激素游离β亚单位对滋养细胞疾病的诊断价值

目的探讨人绒毛膜促性腺激素游离β亚单位(F-βHCG)及F-βHCG/HCG百分比在滋养细胞疾病诊断中的价值.方法应用化学发光免疫测定法测定15例葡萄胎患者清宫前、20例侵蚀性葡萄胎(侵葡)患者及17例绒癌患者未治疗前血清HCG、βHCG及F-βHCG质量浓度(含量),计算F-βHCG/HCG、F-βHCG/βHCG的百分比,并且在治疗期间动态监测其变化.选择同期正常早孕患者40例作为对照组.结果F-βHCG在正常早孕妇女、葡萄胎患者、侵蚀性葡萄胎及绒癌患者的血清平均值分别为(24±11)IU/L、(715±397)IU/L、(69±11)IU/L、(245±229)IU/L.F-βHCG/HCG及F-βHCG/βHCG的百分比在恶性滋养细胞肿瘤患者显著高于葡萄胎及正常早孕妇女(P<0.001).该比值在绒癌患者又高于侵蚀性葡萄胎患者.结论F-βHCG可作为妊娠后判断是正常妊娠,还是滋养细胞疾病的一项监测指标;F-βHCG/HCG、F-βHCG/βHCG的百分比可反映滋养细胞疾病的恶性程度.     

上皮型钙粘附素在正常滋养细胞及妊娠滋养细胞肿瘤组织中的表达

浸润和转移是恶性肿瘤生物学行为最本质的特征 ,涉及癌细胞与细胞外基质相互作用的一系列复杂过程 ,其中细胞粘附是一个重要环节。上皮型钙粘附素 (ｅｐｉｔｈｅｌｉａｌｃａｄｈｅｒｉｎ ,Ｅ ｃｄ)作为钙粘附素家族中的一员 ,为钙依赖性跨膜糖蛋白 ,是介导细胞间联结最重要的一类分子 ,与肿瘤的浸润和转移有着密切的关系[1 ] 。本研究采用免疫组织化学 (组化 )链霉菌抗生物素蛋白 过氧化物酶连接 (ＳＰ)法检测Ｅ ｃｄ在正常滋养细胞、葡萄胎、侵蚀性葡萄胎及绒毛膜癌 (绒癌 )组织中的表达 ,以探讨Ｅ ｃｄ的表达与恶性滋养细胞肿瘤侵袭的关…     

妊娠滋养细胞肿瘤中VEGF CyclinD1的表达及意义

目的　探讨血管内皮生长因子 (VEGF)、细胞周期素D1(CyclinD1)在妊娠滋养细胞肿瘤发生、发展及估计预后中的作用。方法　采用免疫组化S -P法检测VEGF、CyclinD1在正常早孕绒毛及妊娠滋养细胞疾病中的表达。结果　从正常绒毛→葡萄胎→侵蚀性葡萄胎→绒毛膜癌 ,VEGF、CyclinD1表达率逐渐升高。妊娠滋养细胞肿瘤组与正常绒毛、葡萄胎组比较 ,VEGF、CyclinD1的表达率有显著性差异 (P <0 0 5 ,P <0 0 0 1) ;随肿瘤临床期别的增加 ,VEGF、CyclinD1表达率逐渐增高 ,Ⅲ～Ⅳ期与Ⅰ～Ⅱ期比较 ,有非常显著性差异 (P <0 0 0 5 ) ;VEGF与CyclinD1的表达呈正相关 (r =0 483,P <0 0 0 5 )。 结论　VEGF、CyclinD1对预测滋养细胞的恶变 ,判断预后有一定的参考价值。     

TGF-β和IGF表达异常与滋养层相关疾病关系的研究

目的:探讨转化生长因子(TGF-β)和胰岛素样生长因子(IGF)等与滋养层侵入调节密切相关的细胞因子在胎盘绒毛组织中的表达,及与葡萄胎、先兆子痫等滋养层细胞相关妊娠疾病病理机制的关系。方法:采用半定量逆转录多聚酶链反应(RT-PCR)检测方法,分别以正常早孕绒毛和正常足月(自然分娩或剖宫产)胎盘绒毛组织为对照,观察葡萄胎组织与先兆子痫足月胎盘绒毛组织中TGF-β和IGF的表达。结果:5种胎盘绒毛组织中均可检测到IGF-I mRNA的表达,且先兆子痫足月胎盘绒毛组织中IGF-I的表达量明显低于正常足月胎盘绒毛组织,而葡萄胎组织中IGF-I的表达略高于正常早孕绒毛。在3种足月胎盘绒毛组织中可检测到IGF-ⅡmRNA的表达,但相互之间无明显差异。葡萄胎组织中IGF-Ⅱ的表达低于早孕绒毛。5种胎盘绒毛组织中均有TGF-β3的表达,而TGF-β1和TGF-β2的表达并未检测到。在表达量上,葡萄胎组织中TGF-β3的表达明显高于正常早孕绒毛组织,先兆子痫胎盘绒毛组织中TGF-β3的表达强于足月自然分娩的正常胎盘绒毛组织,而剖宫产胎盘绒毛组织中,TGF-β3的表达亦相对较强。结论:TGF-β3和IGF-I在胎盘绒毛组织中的表达变化,可能和葡萄胎、先兆子痫等与滋养层密切相关的妊娠疾病的发生有关。     

HLA-G蛋白在早孕绒毛及葡萄胎中的表达及意义

目的:探讨人类白细胞抗原G(HLA-G)蛋白在早孕绒毛和葡萄胎中的表达及意义。方法:应用免疫组化法检测30例早孕绒毛、20例葡萄胎和11例侵蚀性葡萄胎中HLA-G蛋白的表达情况。结果:①在早孕绒毛,HLA-G蛋白仅表达于绒毛外滋养层细胞,而在其他滋养层细胞则未见表达;②HLA-G蛋白在早孕绒毛、葡萄胎和侵蚀性葡萄胎中表达依次增强,三者比较,差异非常显著(P<0.001)。结论:HLA-G蛋白的表达可能与滋养细胞的侵袭行为有关,在滋养细胞肿瘤的侵袭中有一定作用。     

基质金属蛋白酶及其组织抑制物预测葡萄胎恶变的研究

目的 探讨基质金属蛋白酶（ＭＭＰ－９，ＭＭＰ－２）及其组织抑制物（ＴＩＭＰ－１，ＴＩＭＰ－２）表达量与葡萄胎恶变的相关性。方法 提取组织总ＲＮＡ，应用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）技术检测２２例正常早期妊娠绒毛及３７例葡萄胎组织中ＭＭＰ－９，ＭＭＰ－２、ＴＩＭＰ－１、ＴＩＭＰ－２基因表达量。结果 ＭＭＰ－９、ＭＭＰ－２、ＴＩＭＰ－１及ＴＩＭＰ－２在葡萄胎组织及正常绒毛组织中的表达量差异无显著     

粘附分子CD44V6及抑癌基因PTEN的表达与葡萄胎恶变关系的探讨

目的　探讨粘附分子CD4 4V6及抑癌基因PTEN表达量与葡萄胎恶变的相关性。方法　 1994～ 2 0 0 0年 ,采用免疫组织化学染色技术检测 15例正常绒毛及 5 5例葡萄胎组织中CD4 4V6及PTEN表达 ,应用图像分析系统定量分析其表达水平。结果　CD4 4V6在正常绒毛组织中无表达 ,在葡萄胎非恶变组及恶变组中表达水平均明显高于正常绒毛组织 (P <0 0 1)。在恶变的葡萄胎CD4 4V6表达明显高于未恶变的葡萄胎组织 (P <0 0 1) ;PTEN在葡萄胎非恶变组及恶变组中水平明显低于正常绒毛组织 (P <0 0 1)。PTEN表达量在恶变的葡萄胎组织明显低于未恶变的葡萄胎组织 (P <0 0 1)。结论　CD4 4V6及PTEN的表达可作为预测葡萄胎恶变的新指标     

LMP2和PPM1A在妊娠滋养细胞疾病组织中的表达及其意义

目的 榆测低分子质量多肽2(LMP2)和蛋白磷酸酶1A(PPM1A)在妊娠滋养细胞疾病组织中的表达,并探讨两者在预测葡萄胎恶变中的价值.方法 采用免疫组化EnVision二步法检测196例完全性葡萄胎(其中28例恶变)组织中LMP2和PPM1A蛋白的表达,选择妊娠滋养细胞肿瘤12例(侵蚀性葡萄胎7例、绒毛膜癌5例)和正常妊娠绒毛20例作为对照,回顾性分析其临床病理资料.结果 LMP2和PPM1A存细胞滋养细胞、合体滋养细胞和绒毛外滋养细胞中均有表达.LMP2在葡萄胎恶变者中的表达水平明显高于正常绒毛和葡萄胎良性转归者,分别为(6.79±2.38)、(3.10±1.65)、(5.26±2.63)分,分别比较,差异均有统计学意义(P均<0.01);而与妊娠滋养细胞肿瘤者[(6.42±2.68)分]比较,差异无统计学意义(P=0.113).PPM1A在正常绒毛、葡萄胎(良性转归、恶变)和妊娠滋养细胞肿瘤组织中的表达水平依次下调,分别为(6.30±2.98)、(4.93±2.50)、(4.43±2.04)、(3.33±2.06)分,分别比较,差异均有统汁学意义(P<0.01),且葡萄胎恶变者的表达低于良性转归者(P=0.001).LMP2表达与卵巢黄素化囊肿大小有关,PPM1A表达与子宫大小有关(P<0.05).LMP2与PPM1A的表达水平之间小存在相关性(P>0.05).结论 LMP2高表达和PPM1A低表达可能在滋养细胞的运动、侵袭及葡萄胎的恶性转化中发挥着重要作用.通过检测葡萄胎首次清官术组织中LMP2和PPM1A的表达,对判断葡萄胎的预后有一定的参考意义.

Abstract：

Objective To investigate the expression of low molecular mass polypeptide-2 (LMP2)and protein phosphatase 1A (PPM1A) in gestational trophoblastic disease and elucidate their predictive value in malignant transformation of hydatidiform mole. Methods The expressions of LMP2 and PPM1A protein in 196 complete hydatidiform moles (in which 28 cases with malignant transformation) , 7 invasive moles, 5 choriocarcinomas and 20 normal chorionic villus were detected with the method of En Vision immunohistochemistry. Their clinicopathologic data were retrospectively analyzed. Results LMP2 and PPM1A protein expressed in cytotrophocytes, syncytiotrophoblast and extravillous trophoblast. The level of LMP2 expression in deteriorative hydatidiform mole was significantly higher than that in non-deteriorative hydatidiform mole or normal chorionic villus (6. 79 ±2. 38, 5.26 ±2.63 and 3. 10 ±1.65, all P <0. 01),while there were no difference compared with gestational trophoblastic neoplasms (6. 42 ±2. 68, P=0. 113).The level of PPM1A expression was highest in normal chorionic villus, and decreased gradually in hydatidiform mole (non-deteriorative and deteriorative) and gestational trophoblastic neoplasms (6. 30 ±2. 98, 4. 93 ± 2. 50, 4. 43 ± 2. 04 and 3. 33 ± 2. 06, all P < 0. 01); the level of PPM1A expression in deteriorative hydatidiform mole was significantly lower than that in non-deteriorative hydatidiform mole (P=0.001). The expression of LMP2 protein was correlated to theca lutein ovarian cyst, the expression of PPM1A protein was related with uterine size (P < 0. 05) . While, there was no correlation between the expressions of the two proteins (P >0. 05). Conclusions High expression of LMP2 and low expression of PPM1A might play an important role in the motility and invasiveness of trophohlast cells and malignant transformation of hydatidiform mole. Testing the expression of LMP2 and PPM1A in hydatidiform mole tissues of initial uterine evacuation might be have some reference significance in judging outcomes of hydatidiform mole.     

Circulating placental proteins (hCG, SP1 and PP5) in trophoblastic disease

Summary. Scrum human chorionic gonadotrophin (hCG), pregnancyspecific β₁-glycoprotein (SP₁) and placental protein 5 (PP5) levels have been measured by radioimmunoassay in 20 patients (116 samples) with hydatidiform mole, one patient (nine samples) with invasive mole and 10 patients (103 samples) with choriocarcinoma. Measurement of both serum SP₁ and hCG are useful in the monitoring of these diseases. The presence of PP5 in hydatidiform mole and its absence in choriocarcinoma support the hypothesis that PP5 is closely associated with the invasive activity of malignant trophoblast.     

妊娠滋养细胞疾病组织中HIF-1α、VEGF的表达及临床意义

目的：检测缺氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）在正常早孕绒毛、葡萄胎和妊娠滋养细胞肿瘤（GTN）组织中的表达情况,并探究其临床意义。方法：收集正常早孕绒毛组织20例（正常早孕绒毛组）、葡萄胎组织35例（葡萄胎组）和GTN组织28例[包括侵蚀性葡萄胎组织14例（侵蚀性葡萄胎组）,绒毛膜癌组织14例（绒毛膜癌组）]。采用免疫组化法检测各组织样本中HIF-1α和VEGF的蛋白表达情况。分析GTN患者不同年龄及FIGO分期组织中HIF-1α和VEGF表达的情况。分析GTN组织样本中HIF-1α和VEGF表达的关系。结果：正常早孕绒毛组与葡萄胎组HIF-1α和VEGF蛋白表达的阳性率比较,差异无统计学意义（均P＞0.05）;正常早孕绒毛组HIF-1α和VEGF蛋白表达的阳性率低于侵蚀性葡萄胎组和绒毛膜癌组,差异有统计学意义（均P＜0.05）;侵蚀性葡萄胎组和绒毛膜癌组HIF-1α和VEGF蛋白表达的阳性率比较,差异无统计学意义（均P＞0.05）。GTN患者FIGO Ⅲ+Ⅳ期组HIF-1α和VEGF蛋白表达的阳性率高于Ⅰ+Ⅱ期组,差异有统计学意义（均P＜0.05）;而不同年龄GTN患者HIF-1α和VEGF蛋白表达的阳性率比较,差异无统计学意义（均P＞0.05）。HIF-1α与VEGF在GTN组织中的表达呈正相关（rs=0.995,P=0.000）。结论：HIF-1α及VEGF可能在GTN发生和恶性进展过程中发挥协同作用。     

Molecular weight and fragmentation of human chorionic gonadotropin in urine in patients with trophoblastic diseases

Molecular weights (MW) of urinary human chorionic gonadotropin (hCG) from trophoblastic diseases were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by Western blotting using specific antibodies. Although the MW of hCG beta from hydatidiform mole and invasive mole were identical to that of standard hCG beta, those from choriocarcinoma were individually different. These results indicate that the structural changes of carbohydrates, which may be induced by malignant transformation of trophoblast, can be reflected as differences in MW. In SDS-PAGE under nonreducing conditions. Western blotting using anti-hCG beta-carboxy-terminal peptides (CTP) revealed a single band corresponding to hCG beta. Under reducing conditions with dithiothreitol (DTT), however, a second low MW material (CTP') could be observed with anti-hCG beta-CTP. All hCG samples from invasive mole and choriocarcinoma were much more susceptible than standard hCG to release of CTP' by DTT. Estimation of MW and susceptibility to DTT reducing of urinary hCG by Western blotting are useful in the diagnosis of invasive mole and choriocarcinoma.     

Gestational trophoblastic disease in women aged 50 or more

Twenty cases of gestational trophoblastic disease in women aged 50 or more are reported. The lesions were 7 hydatidiform mole (35%), 8 invasive mole (40%), and 5 choriocarcinoma (25%). The most common presenting symptom was abnormal vaginal bleeding. Three choriocarcinoma patients were postmenopausal and all of them had choriocarcinoma. None of the patients with hydatidiform mole or invasive mole died of the disease, but 4 of 5 choriocarcinoma patients died of the disease. Because of the high rate (56.3%) of malignant sequelae after molar evacuation, a primary hysterectomy for the treatment of hydatidiform mole in this age group is recommended. It is important to maintain a high level of suspicion for the diagnosis of gestational trophoblastic disease in the elderly women.     

Diagnostic reliability of simultaneous measurements of beta human chorionic gonadotropin and pregnancy-specific beta-1-glycoprotein in serum of patients with trophoblastic disease

Serum levels for beta-human chorionic gonadotropin (beta-hCG) and pregnancy-specific beta 1-glycoprotein (SP1) in patients with trophoblastic disease were measured by radioimmunoassay and enzyme-linked immunosorbent assay. The beta-hCG:SP1 ratios were below 1.0 in all 22 cases of complete hydatidiform mole and in 8 of 9 cases of partial hydatidiform mole. Two (10.5%) of 19 cases of invasive mole involving metastasis had ratios that rose above 1.0 during chemotherapy. Ratios ranged from 1.6 to 29 in 11 of 15 cases of choriocarcinoma before chemotherapy. The remaining 4 cases, diagnosed within 3 months of antecedent pregnancy, had ratios below 0.99. Thus, the difference between choriocarcinoma and nonchoriocarcinoma beta-hCG:SP1 ratios may be due to trophoblastic differentiation based on the developmental stage and with trophoblast age, or due to the mass and potential activity of trophoblastic cells.