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．     

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     

c-erbB2、nm23-H1在妊娠滋养细胞疾病中的表达及其临床意义

目的 :探讨癌基因c erbB2和抑癌基因nm2 3 H1在妊娠滋养细胞肿瘤的临床分期及临床主要预后因素不同的情况下表达的差异 ,以期达到对妊娠滋养细胞疾病转归的预测。方法 :采用针对两种基因表达产物的单克隆抗体进行SABC免疫组织化学染色 ,回顾性检测分析 30例不同妊娠期正常胎盘、2 1例葡萄胎、2 1例侵蚀性葡萄胎及 2 0例绒癌中两种基因产物的表达情况。结果 :c erbB2基因在侵蚀性葡萄胎和绒癌中的表达明显高于葡萄胎及妊娠中晚期正常胎盘 ,而nm2 3 H1的表达明显低于葡萄胎及妊娠中晚期正常胎盘 (P <0 0 5 ) ;c erbB2基因在临床Ⅲ、Ⅳ期患者中的表达高于Ⅰ、Ⅱ期患者 ,但差异无统计学意义 ;nm2 3 H1基因产物的高表达与WHO预后评分系统的好的预后因素相一致。结论 :c erbB2的高表达及nm2 3 H1的低表达与葡萄胎恶变紧密相关 ,对于妊娠滋养细胞肿瘤的早期诊断、早期治疗及预后评估具有重要的临床意义。     

p53基因突变对预测葡萄胎恶变的初步研究

随着人们对肿瘤分子生物学认识的不断深入 ,已知癌基因的激活和抑癌基因的失活对肿瘤的发生发展起重要作用。ｐ5 3基因是一种肿瘤抑制基因 ,在肝癌、肺癌、乳腺癌、胃癌、卵巢癌等肿瘤中有突变失活[1] 。而在葡萄胎组织中ｐ5 3基因突变与恶变的关系研究较少 ,尚无定论。本研究采用聚合酶链反应 单链构象多态分析 (ＰＣＲ ＳＳＣＰ)技术检测葡萄胎组织中ｐ5 3基因第 5～ 8外显子突变情况 ,并结合患者的临床随访结果进行初步研究。现报道如下。一、资料与方法1.资料来源与分组 :收集 1992～ 1996年在我院住院清宫的葡萄胎患者 2 0例 ,根据 2…     

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。     

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。     

葡萄胎恶变预测及预后研究的进展

近来对葡萄胎恶变因素已有新认识。血、尿hCG测定有助于诊断葡萄胎及判断其性质。葡萄胎细胞遗传学特别是新人类肿瘤学在预测葡萄胎恶变、估计预后等方面取得了新进展。新的诊断技术,如影象分析术、聚合酶链反应及流式细胞分析技术等也在不断发展。DNA及RNA含量可能成为提示葡萄胎预后的重要指标,流式细胞分析技术是达到这一目的的良好手段。     

卵巢子宫内膜样癌p53抑癌基因蛋白的表达

卵巢子宫内膜样癌ｐ５３抑癌基因蛋白的表达冷金花，郎景和，郭丽娜，沈铿，许秀英本研究通过检测２８例卵巢子宫内膜样癌ｐ５３抑癌基因的表达情况，以探讨ｐ５３与卵巢子宫内膜样癌临床和病理表现的关系以及对预后的影响。一、材料和方法１．临床资料及组织标本：我院１...     

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     

不同类型卵巢浆液性囊腺肿瘤p53抑癌基因蛋白的表达

不同类型卵巢浆液性囊腺肿瘤ｐ５３抑癌基因蛋白的表达刘节，杨淑杰本研究应用ｐ５３单克隆抗体以ＡＢＣ免疫组化技术检测ｐ５３蛋白在卵巢肿瘤组织中表达情况，以探讨其分布规律及临床意义。一、材料与方法１．标本：收集我院１９８５～１９９２年间卵巢浆液性囊腺肿瘤标...     

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.     

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.     

正常胎盘及葡萄胎滋养细胞H—ras和C—myc基因产物表达

目的：探索ｒａｓ、ｍｙｃ基因蛋白在正常胎盘发育中的作用及ｒａｓ、ｍｙｃ基因蛋白表达与葡萄胎临床预后关系。方法：用免疫组化方法，分析４０例正常胎盘及５０例葡萄胎组织Ｈ－ｒａｓ和Ｃ－ｍｙａ基因蛋白表达情况。结果：孕早期胎盘ｒａｓ、ｍｙｃ基因蛋白的表达部位主要在细胞滋养细胞，表达率分别为７０％和８０％，孕早期表达部位主要在全体滋养细胞，表达率逐渐降低，足月时表达消失。葡萄胎ｒａｓ、ｍｙｃ基因蛋白表达率分     

葡萄胎患者清宫化疗后再次妊娠适宜时间的探讨

目的 :探讨葡萄胎患者清宫、预防性化疗后再次妊娠的适宜时间。方法 :为1988年 1月至 1995年 1月住院的葡萄胎患者制定系统化治疗方案 ,出院后定期随访 ,根据清宫后再次妊娠的时间分为 3组 ,分别观察对母婴健康的影响。结果 :清宫后 7～ 2 4个月妊娠者与清宫后超过 2 4个月妊娠者母婴健康情况差异无显著性 (P >0 .0 5 )。结论 :葡萄胎患者治疗后 ,β HCG降至正常水平 ,持续半年 ,又无异常临床表现 ,希望妊娠者可解除避孕措施。     

家系成员中有葡萄胎史的六例葡萄胎患者的家系分析及NLRP7基因突变的评估

目的 对家系成员中有葡萄胎史的葡萄胎患者进行家系分析,并评估其NLRP7基因的突变情况.方法 选取2003年1月至2010年12月在浙江大学医学院附属妇产科医院及山东枣庄矿业集团中心医院就诊的家系成员中有葡萄胎史的葡萄胎患者6例,进行家系分析;以2003年1月至2010年12月在浙江大学医学院附属妇产科医院体检的健康妇女60例为对照,抽取葡萄胎患者及其相关家系成员和健康妇女的外周静脉血,提取DNA,采用PCR扩增、测序及序列比对分析,对NLRP7基因突变进行筛选及分析,寻找突变位点及对应的核苷酸变异和蛋白质变异.结果 家系成员中有葡萄胎史的6例葡萄胎患者中,3个家系是患者的姐妹有葡萄胎史,其中2个家系(家系MoCh76和Ch77)为家族性复发性葡萄胎,这2个家系中患者的NLRP7基因均存在2个位点的突变,家系MoCh76中患者的突变位点为外显子3、5,对应的核苷酸变异分别为[295G＞T]、[1970A＞T],蛋白质变异分别为[Glu99X]、[Asp657Val],家系Ch77中2个反复发生葡萄胎的姐妹的突变位点为外显子4、7,对应的核苷酸变异分别为[1294C＞T]、[247l+1G＞A],蛋白质变异分别为[Arg432X]、[Leu825X];1个家系(家系105)为非家族性复发性葡萄胎,患者未发现NLlP7基因的突变位点及对应的核苷酸变异和蛋白质变异.3个家系是患者的母亲有葡萄胎史,均为非家族性复发性葡萄胎,家系MoCh73的患者存在NLRP7基因单个位点的突变,突变位点为外显子4,对应的核苷酸变异为[1137G＞C]、蛋白质变异为[Lys379Asn];家系106和110的患者均未发现NLRP7基因的突变位点及对应的核苷酸变异和蛋白质变异.60例健康对照妇女均未发现NLRP7基因的上述突变位点及对应的核苷酸变异和蛋白质变异.结论 NLRP7基因突变可能是导致家族性复发性葡萄胎的相关基因.

Abstract：

Objective To evaluate the NLRP7 gene mutations and variants and their expression of genetic approach in hydatidiform mole patients with family history.Methods Six cases of mole patients with family members of mole history and 60 healthy women, taking blood, extracting DNA, the genetic mutation on NLRP7 screening and analysis, looking for mutations and corresponding amino acids, proteins control gene mutation found NLRP7 area.Results In 6 mole patients with family history:three patients were with sister's history of mole, and 2 of them familial recurrent hydatidiform mole(from family MoCh76 and family Ch77), there are 2 loci NLRP7 gene mutation.Screening patients from family MoCh76 for mutations in NLRP7 revealed in exon 3 and exon 5, amino acids [295G ＞ T] and [1970A ＞ T], proteins [Glu99X] and [Asp657Val], in a heterozygous.Screening patients from family Ch77 for mutations in NLRP7 revealed in exon4 and exon 7, amino acids [1294C ＞ T] and [2471 + 1G ＞ A], proteins [Arg432X] and [Leu825X], in a heterozygous.Screening patients from family 105 for mutations in NLRP7 revealed no NLRP7 gene mutation.There were mother's history of mole in three patients, and they were not familial recurrent hydatidiform mole.Screening patients from family MoCh73 for mutations in NLRP7revealed in exon 4, amino acids [1137G ＞ C], proteins [Lys379Asn], in a heterozygous.Screening patients from family 106 and family 110 for mutations in NLRP7 revealed no NLRP7 gene mutation.There were not found mutations and variations in 60 cases of ethnic matched control group.Conclusion NLRP7 mutations may be lead to familial recurrent hydatidiform mole.