c—Ha—ras,c—erbB2癌基因产物和p53,nm23抑癌基因产物对葡萄？…

目的：探讨ｃ－Ｈａ－ｒａｓ，ｃ－ｅｒｂＢ２癌基因产物和ｐ５３ｎｍ２３抑癌基因产物表达异常和葡萄胎恶变的关系及在预测葡萄胎恶变的价值。方法：采用针对４种基因产物的单克隆抗体，ＳＰ法免疫组织化学染色，回顾分析了≥２ａ随访证实发生恶变的葡萄胎５０例（恶变组）和未发生恶变的葡萄胎３２例（非恶变组）中４种基因产物的表达情况，结果：恶变组中ｃ－Ｈａ－ｒａｓ和ｎｍ２３基因产物的表达程度显著低于非恶变组（Ｐ〈０．     

癌基因,妊娠性滋养细胞增民葡萄胎恶变关系的研究

目的：探讨癌基因、妊娠性滋养细胞增生程度与葡萄胎恶变的关系。方法：采用针对Ｃ－Ｈａ－ｒａｓ及Ｃ－ｅｒｂＢ２基因表达产物Ｐ＾２１和Ｐ＾１８５的单克隆抗体进行免疫组织化学染色。检测８２例葡萄胎中两种基因产物的表达情况，经２年以上随访证实未发生恶变３２例为非恶性变组，经手术和临床证实发生恶变５０例为恶变组，其中３５例行手术治疗。     

癌基因、妊娠性滋养细胞增生与葡萄胎恶变关系的研究

目的：探讨癌基因、妊娠性滋养细胞增生程度与葡萄胎恶变的关系。方法：采用针对Ｃ－Ｈａ－ｒａｓ及Ｃ－ｅｒｂＢ２基因表达产物Ｐ２１和Ｐ１８５的单克隆抗体进行免疫组织化学染色。检测８２例葡萄胎中两种基因产物的表达情况，经２年以上随访证实未发生恶变３２例为非恶变组，经手术和临床证实发生恶变５０例为恶变组，其中３５例行手术治疗。结果：恶变组Ｐ２１的表达程度低于非恶变组（Ｐ＝０．００８２）；Ｐ１８５的表达显著高于非恶变组（Ｐ＝０．００２８）。手术治疗的３５例中，恶变后两种基因产物的表达改变较恶变前更明显。两组葡萄胎中滋养细胞增生程度差异无显著性（Ｐ＝０．４１３）。不同来源的绒毛膜癌（绒癌）之间及绒癌与侵蚀性葡萄胎（侵葡）之间，Ｐ２１和Ｐ１８５的表达差异亦无显著性（Ｐ＝０．２６８，Ｐ＝０．７１９）。结论：Ｐ２１的低表达及Ｐ１８５的高表达与葡萄胎恶变有关，但与其恶性转化方向无关；滋养细胞增生程度与葡萄胎恶变亦无关。     

卵巢癌组织中多种癌基因蛋白同时表达的临床意义

卵巢癌组织中多种癌基因蛋白同时表达的临床意义李广太焦书竹岳晓莉牛春莲李红宇王振琴同时检测１０３例卵巢癌组织癌基因ｎｅｕ和ｒａｓ、抑癌基因ｐ５３和ｐ１６、抗凋亡基因ｂｃｌ２和转移抑制基因ｎｍ２３等６种癌蛋白（ｏｎｃｏｐｒｏｔｅｉｎ）的变化，探讨这些...     

癌基因bcl-2及抑癌基因p53在子宫内膜癌的表达及临床意义

目的：研究癌基因ｂｃｌ－２及抑癌基因ｐ５３在子宫内膜癌发生、发展中的作用。方法：采用免疫组化ＡＢＣ法检测４９例子宫内膜癌中ｂｃｌ－２、ｐ５３基因蛋白的表达。结果：４９例子宫内膜癌中２６例ｂｃｌ－２表达阳性，占５３％；１２例ｐ５３表达阳性，占２５％。子宫内膜癌组织学分级Ｇ１、Ｇ２ｂｃｌ－２表达率（６６％）显著高于Ｇ３表达率（２１％，Ｐ＜００５），而Ｇ３ｐ５３表达率（４６％）显著高于Ｇ１、Ｇ２表达率（１７％，Ｐ＜００５），ｂｃｌ－２表达阳性与阴性者生存率统计无显著性差异，ｐ５３表达阳性者生存率显著低于ｐ５３表达阴性者。ｂｃｌ－２、ｐ５３表达与肌层浸润、手术分期无明显相关。结论：癌基因ｂｃｌ－２与抑癌基因ｐ５３可能在子宫内膜癌发生的不同阶段起作用，抑制细胞凋亡，促进肿瘤的发展与转归。     

p~(53)与C-erbB_2、C-ras、C-myc在卵巢粒层细胞瘤中的过度表达及其临床意义

目的：了解ｐ５３及Ｃ－ｅｒｂＢ２、Ｃ－ｒａｓ、Ｃ－ｍｙｃ在卵巢粒层细胞瘤中的表达及与此瘤发生、发展的关系。方法：采用单克隆抗体免疫组化技术，对２５份卵巢粒层细胞瘤组织进行ｐ５３、Ｃ－ｅｒｂＢ２、Ｃ－ｒａｓ及Ｃ－ｍｙｃ表达的检测，分析基因表达与临床－病理指标及患者预后的关系。结果：２５例卵巢粒层细胞瘤中ｐ５３、Ｃ－ｅｒｂＢ２、Ｃ－ｒａｓ、Ｃ－ｍｙｃ的过度表达率分别为５６％、５６％、４８％、４８％。Ⅲ～Ⅳ期ｐ５３的过度表达高于Ⅰ～Ⅱ期；有残余瘤者较无残余瘤者显著增高。Ⅲ～Ⅳ期的Ｃ－ｅｒｂＢ２过度表达率显著高于Ⅰ～Ⅱ期者。高分化组的Ｃ－ｒａｓ基因过度表达率显著高于低分化组。未发现Ｃ－ｍｙｃ的表达与临床－病理各指标有关。两种及两种以上基因同时表达者显著高于单基因表达者。ｐ５３与Ｃ－ｅｒｂＢ２及Ｃ－ｍｙｃ过度表达间呈正相关。临床分期及Ｃ－ｅｒｂＢ２的过度表达是独立影响患者预后的因素。结论：ｐ５３及Ｃ－ｅｒｂＢ２、Ｃ－ｒａｓ、Ｃ－ｍｙｃ的表达对卵巢粒层细胞瘤的发生、发展及患者预后有一定的影响。     

癌基因,抑癌基因与卵巢癌基因治疗

肿瘤发生是多基因参与的过程，目前已发现癌基因Ｋ－ｒａｓ的突变、ｃ－ｍｙｃ和ｃ－ｅｒｂＢ－２的扩增和过度表达以及抑癌基因ｐ５３的突变与卵巢癌紧密相关。基因治疗是卵巢癌治疗的最新策略。在基因表达成为蛋白的三个环节：ＤＮＡ、ｍＲＮＡ和蛋白质水平上，人们分别提出了三链寡聚核苷酸链、反义寡聚核苷酸链与核酶、以及单链抗体的方法进行基因治疗。这些方法的发展与完善，将使巢癌的基因治疗成为现实。     

P^53与C—erbB2,C—ras,C—myc在卵巢粒层细胞瘤中的过度表达及…

目的：了解ｐ＾５３及Ｃ－ｅｒＢ２，Ｃ－ｒａｓ，Ｃ－ｍｙｃ在卵巢粒层细胞瘤中的表达及此瘤发生，发展的关系，方法：采用单克隆抗体免疫组化技术，对２５份卵巢粒层细胞瘤组织进行ｐ＾５３，Ｃ－ｅｒＢ２，Ｃ－ｒａｓ及Ｃ－ｍｙｃ表达的检测，分析基因表达与临床一病理指标及患者预后的关系，结果：２５例卵巢粒层细胞瘤中，Ｐ＾５３，Ｃｅｒｂ２，Ｃ－ｒａｓ，Ｃ－ｍｙｃ的过度表达率分别为５６％，５６％，４８％，４８％，Ⅲ～     

C-erbB_2、p16基因在卵巢肿瘤中的表达及其临床意义的研究

目的：探讨卵巢肿瘤中癌基因Ｃ－ｅｒｂＢ２及抑癌基因ｐ１６的表达及其与临床病理特征及患者预后的关系。方法：用免疫组化ＡＢＣ法，分析４９份卵巢恶性肿瘤、１２份交界性肿瘤、１５份良性肿瘤石蜡包埋组织中Ｃ－ｅｒｂＢ２、ｐ１６的表达情况。结果：①在卵巢恶性肿瘤、交界性肿瘤、良性肿瘤之间Ｃ－ｅｒｂＢ２的表达差异有显著性（Ｐ＜０．０１）。Ｃ－ｅｒｂＢ２的表达率及表达强度与组织分化程度患者及生存期有显著相关性（Ｐ＜０．０５），Ｃ－ｅｒｂＢ２的过度表达见于恶性程度高、组织分化差、患者预后不良的肿瘤中。②在卵巢恶性肿瘤、交界性肿瘤、良性肿瘤之间ｐ１６的表达差异有显著性（Ｐ＜０．０１）。其表达强度与组织分化程度及临床分期有显著相关性，在恶性程度较高、组织分化差、较晚期的肿瘤中ｐ１６的表达较弱。结论：癌基因Ｃ－ｅｒｂＢ２及抑癌基因ｐ１６在卵巢癌组织中广泛存在，并与其临床病理指标之间有一定的相关性，提示这些基因在卵巢癌的发生、发展中起一定作用，并对患者预后的判断及治疗有一定的指导意义。对各基因之间复杂的相互作用、协同作用有待进一步研究。     

C—erbB2,nm23和p53蛋白在卵巢上皮性癌中的表达及其临？…

目的 探讨Ｃ－ｅｒｂＢ２、ｎｍ２３和ｐ５３ ３种基因蛋白在卵巢上皮性癌中表达的关系。方法 应用链霉菌抗生物素蛋白－过氧化酶连接法检测７０例放巢上皮性癌石蜡切片中Ｃ－ｅｒｂＢ２、ｎｍ２３和ｐ５３蛋白的表达情况。应用Ｋａｐｌａｎ－Ｍｅｉｅｒ法及多变量Ｃｏｘ比例风险回归模型，分析这３种蛋白表达与患者预后的关系。结果 （１）Ｃ－ｅｒｂＢ２蛋白表达率为３１．４％，与其临床分期有关；ｎｍ２３蛋白表达率为３８．     

The relationship between expression of c-ras,c-erbB-2, nm23, and p53 gene products and development of trophoblastic tumor and their predictive significance for the malignant transformation of complete hydatidiform mole

OBJECTIVE: The aims of this retrospective study by means of immunohistochemical staining were (1) to study the expression of c-ras, c-erbB-2, p53, and nm23 gene products in complete hydatidiform moles that progress to gestational trophoblastic tumor and in those that remit spontaneously after evacuation, and (2) to estimate the predictive value of the expression of these four gene products in malignant transformation of complete hydatidiform mole. METHODS: Clinical data of patients with complete hydatidiform mole were obtained by retrospective chart review. Formalin-fixed paraffin sections of 50 cases of complete mole that progressed to gestational tumor and 32 cases of complete mole that remitted spontaneously were studied immunohistochemically for c-ras, c-erbB-2, p53, and nm23 proteins. The prognostic value of the proteins for the malignant transformation of complete mole was analyzed by multiple logistic regression and stepwise logistic estimation. Sections of 30 cases of invasive mole and 19 cases of choriocarcinoma were also immunohistologically studied for expression of the proteins. RESULTS: Expression of c-erbB-2 and p53 gene products was significantly increased and expression of nm23 and c-ras products was remarkably decreased in complete hydatidiform moles that progressed into postmolar tumor compared with those that remitted spontaneously after evacuation. There was no significant difference in the expression of the four genes in invasive mole and in choriocarcinoma. A logistic estimation model for predicting malignant transformation of complete mole was established based on the expression of gene products. When the expression of four gene products was used, the predictive sensitivity of the regression model was 86.0%, and the specificity was 75.0%. The positive predictive value was 84.3%, the negative predictive value was 77.4%. Logistic stepwise regression analysis showed that the altered expression of c-erbB-2 and nm23 products had strong predictive value, while the expression of c-ras and p53 products had no significant predictive value for the malignant transformation of complete mole. CONCLUSION: The altered expression of c-ras, c-erbB-2, nm23, and p53 gene products may be important in the pathogenesis of gestational trophoblastic tumor. The decreased expression of nm23 protein and increased expression of c-erbB-2 protein are strong predictors for the malignant transformation of complete mole.     

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.     

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。     

Correlation of c-erbB-2 oncogene and p53 tumor suppressor gene with malignant transformation of hydatidiform mole

AIM: Considering the roles of c-erB-2 and p53 oncoproteins in tumor progression, we aimed to evaluate their expression in hydatidiform moles, and the possible predictive value of this immunoexpression in postmolar follow-up. METHODS: Group I comprised 35 patients with progression to gestational trophoblastic tumor, and group II included 32 patients with progression to spontaneous remission. Immunohistochemical tests were performed by streptavidin-peroxidase method. c-erbB-2 immunoexpression was evaluated according to quantitative and semiquantitative criteria; p53 according to percentage of cells with stained nuclei. Data were analyzed by Student t-test, Mann-Whitney test, ROC curve and logistic regression analysis. RESULTS: c-erbB-2 and p-53 expressions were significantly increased in group I. Quantitative and semiquantitative analysis of c-erb-2 showed that its expression may be associated with mole hydatidiform progression to gestational trophoblastic tumor. Taking into account cells with complete membranous delineation we proposed a cut-off value of 10.8%. Similarly, considering the percentage of cells presenting nuclei marked by p53 we suggested a cut-off value of 40.1% for the prediction of malignant transformation of mole hydatidiform. CONCLUSIONS: c-erbB-2 and p53 immunoexpression in hydatidiform mole are usually increased with malignant transformation. In addition to beta-fraction of human chorionic gonadotropin, they could possibly help the establishment of a therapeutic protocol.     

Expression of nm23-H1 protein in relation to myometrial invasion in complete hydatidiform moles

OBJECTIVE: Although nm23-H1 protein expression has been related to invasion in many cancers, its expression and prognostic significance in complete hydatidiform moles has not yet been investigated. The search for biologic parameters in molar placentas, which are useful for identifying patients who show myometrial invasion of the tumor, is crucial. We examined the clinical significance of nm23-H1 expression in complete hydatidiform mole. METHODS: Sections of 105 cases of complete hydatidiform moles (including 25 cases of invasive mole) and 95 cases of gestational age--matched normal placentas were immunohistochemically stained with anti-nm23-H1 antibody, which recognizes the nm23-H1/NDP kinase A gene product. RESULTS: Expression of nm23-H1 was detected in the cytotrophoblasts and syncytiotrophoblasts of molar placentas and normal placentas, whereas it was not detected in stromal tissue. Expression of nm23-H1 showed a negative relation to invasion, suggesting its use as a potential marker of myometrial invasion in complete hydatidiform moles. CONCLUSION: nm23-H1 expression could be used as a marker for accurate evaluation of myometrial invasion in complete hydatidiform mole.     

葡萄胎p53、p21~(CIP1)及p185蛋白表达与恶变的关系

目的 :探讨葡萄胎p5 3、p2 1CIP1及p185蛋白表达与恶变的关系及其临床特点。方法 :免疫组化法检测葡萄胎标本中p5 3、p2 1CIP1及p185蛋白的表达 ,以侵蚀性葡萄胎及绒癌为对照 ,并回顾性分析其临床资料。结果 :葡萄胎组p5 3、p2 1CIP1、p185蛋白阳性表达率分别为 35 % (35 / 10 0 ) ,71% (71/ 10 0 )及 36 % (36 / 10 0 ) ,与恶性对照组相比均有显著性差异 (P <0 .0 5 ) ;而完全性与部分性葡萄胎 ,完全性葡萄胎恶变组与非恶变组之间差异均无显著性 (P >0 .0 5 ) ,但恶变组p2 1CIP1表达有降低趋势。结论 :p5 3、p2 1CIP1及p185蛋白表达改变与葡萄胎恶变无确定关系 ,但可作为晚期现象出现于恶性滋养细胞肿瘤中 ,其中p2 1CIP1蛋白表达降低提示滋养细胞有向恶性转化的倾向     

Expression of the p53 gene and apoptosis in gestational trophoblastic disease

In order to understand the involvement of the p53 tumour suppressor gene in the pathogenesis of gestational trophoblastic disease (GTD), we investigated its genetic status, protein expression and its role in apoptosis in samples of complete and partial hydatidiform mole as compared with those of normal placenta. Direct sequencing of polymerase chain reaction (PCR) products of the coding and non-coding regions of the p53 gene demonstrated no mutations in any of the studied samples. Immunohistochemical studies revealed increased expression of the p53 protein predominantly in the nuclei of villous cytotrophoblasts. This over-expression of p53 was found in all samples of complete mole, in 50 per cent of partial mole samples and in about 30 per cent of normal placenta cases, although no significant difference in the staining intensity and pattern was observed. An in situ detection of DNA nicking (TUNEL) staining, demonstrating apoptosis, was also detected predominantly in villous cytotrophoblasts and in stromal areas. The per centage of apoptotic cells in all studied samples, determined by flow cytometry, demonstrated a significant increase in apoptotic cells in samples of complete and partial hydatidiform mole compared with those of normal placenta (P< 0.0003 and P< 0.004, respectively).In conclusion, the current study may provide a possible explanation to the pathogenesis of GTD, probably associated with extensive p53-dependent apoptosis to modulate excessive trophoblastic proliferation.     

P^21ras c—mycp53和雌孕激素受体在子宫内膜癌的表达

应用免疫组化ＬＳＡＢ法，对３２例子宫内膜癌，６例腺瘤型增生，２０例腺囊型增生组织的癌基因Ｐ＾２１ｒａｓ，ｃ－ｍｙｃ及抑癌基因ｐ５３蛋白表达进行了检测，对３２例子宫内膜癌进行了雌，孕激素受体的检测，并对子宫内膜癌组织Ｐ＾２１ｒａｓ，ｃ－ｍｙｃｐ５３过度表达与雌，孕激素受体的关系了分析，结果显示：Ｐ＾２１ｒａｓｃ－ｍｙｃｐ５３在子宫内膜癌组织中的阳性表达率分别为５９．４％，６２．５％和１８．８％，雌，