层粘连蛋白和纤维粘连蛋白在正常绒毛膜葡萄胎,绒毛膜癌组织中？…

目的：探讨层粘连蛋白和纤维粘连蛋白在正常绒毛膜和滋养细胞肿瘤中的作用。方法：用免疫组织化学方法观察层粘连蛋白和纤维连蛋白在正常绒毛膜、葡萄胎和绒毛膜癌组织中的表达。结果：在正常绒毛膜组织中,二种蛋白有广泛表达,如绒毛上皮基膜、毛细血管内皮基膜、绒毛间质、滋养细胞柱和蜕膜。在葡萄胎,层粘连蛋白分布于绒毛上皮基膜和蜕膜组织,在基膜中表达强度有所不同;纤维粘连蛋白分布于绒毛和蜕膜内,呈弱阳性表达,在侵蚀     

层粘连蛋白与葡萄胎及侵蚀性葡萄胎相关性的免疫组化研究

为了探讨层粘连蛋白（ＬＮ）在非侵蚀性（ＨＭ）和侵蚀性葡萄胎（ＩＨＭ）的发生和转化过程中的作用，本研究采用免疫组化法，观察了ＬＮ在ＨＭ和ＩＨＭ的分布。结果显示：ＬＮ在葡萄胎中的游离绒毛合体滋养细胞（ＬＮＲ）呈阳性着色、ＬＮ呈阴性；游离绒毛细胞滋养细胞ＬＮ呈阴性；游离绒毛细胞滋养层基底膜ＬＮ呈阴性；游离绒毛基质细胞ＬＮ呈阴性；绒毛外滋养细胞ＬＮ呈阴性；绒毛外滋养细胞基底膜ＬＮ呈弱阳性；固定绒毛柱滋养细胞ＬＮ呈阴性；近绒毛滋养层柱基底膜ＬＮ呈弱阳性；远绒毛滋养层柱基底膜ＬＮ呈弱阳性。在侵蚀性葡萄胎中游离绒毛合体滋养细胞、游离绒毛细胞滋养细胞、游离绒毛细胞滋养层基底膜和游离绒毛基质细胞ＬＮ呈阴性；绒毛外滋养细胞和绒毛外滋养细胞基底膜ＬＮ呈强阳性；固定绒毛柱滋养细胞ＬＮ呈阴性     

Beclin-1在妊娠滋养细胞疾病中的表达意义

目的探讨Beclin-1在妊娠滋养细胞疾病中的表达意义。方法收集正常绒毛、葡萄胎、侵蚀性葡萄胎、绒毛膜癌、上皮样滋养细胞肿瘤和胎盘部位滋养细胞肿瘤组织共150例,采用免疫组织化学方法检测并分析各组组织中Beclin-1蛋白的表达水平。结果 Beclin-1在绒毛膜癌和侵袭性葡萄胎中的表达水平显著高于葡萄胎和正常绒毛(P0.05);化疗耐药的妊娠滋养细胞肿瘤病例中Beclin-1高表达,且与妊娠滋养细胞肿瘤的分期无明显相关性(P0.05)。结论 Beclin-1可能在妊娠滋养细胞疾病的进展和化疗耐药中起重要作用,有望成为判断葡萄胎恶变的辅助指标和化疗耐药评估候选指标之一。     

层粘连蛋白和纤维粘连蛋白在神经管畸形发生中的作用──免疫组织化学研究

给妊娠金黄地鼠灌服过量维生素Ａ酸后，在不同时间剖腹取胎，石蜡包埋、连续切片。用免疫组织化学方法，对神经上皮及其基膜、脊索和神经管周围间充质中的基质粘着分子——纤维粘连蛋白和层粘连蛋白进行定性、定位和半定量观察。结果显示，实验组各组胚胎的纤维粘连蛋白和层粘连蛋白的免疫组织化学染色均有不同程度的减弱。说明过量维生素Ａ酸可使神经上皮及其基膜和周围间充质中的纤维粘连蛋白和层粘连蛋白降低，从而干扰了神经上皮细胞的正常增殖、迁移、生理性死亡和细胞粘着过程。这是维生素Ａ引起神经管畸形的一个重要途径。     

层粘连蛋白和纤维粘连蛋白在正常绒毛膜组织中的表达

层粘连蛋白和纤维粘连蛋白是细胞外基质的重要成分 ,在正常组织中有广泛分布。目前认为层粘连蛋白有 10条不同源的多肽链 ,构成 11种不同的蛋白分子。纤维粘连蛋白的结构具有多形性 ,主要由 ED-A、ED- B、 CS三个结构区不同的拼接方式所决定。层粘连蛋白和纤维粘连蛋白不仅在支持、连接和维持组织形态 ,调节细胞的粘附、生长、分化、增殖等方面起重要作用 ,而且与胚泡着床及胎盘的形成也有密切关系     

层粘连蛋白和纤维粘连蛋白在过量维生素A酸致心脏畸形中的作用： …

维生素Ａ酸是常见的一类化学致畸因子，可引起各种心脏畸形，如主动脉骑跨，室间隔缺损等，实验采用免疫组织化学方法观察层粘连蛋白和纤维连蛋白在心脏正常和异常发育过程 的分布和变化规律，以探讨过量维生素Ａ酸致心脏畸形发生的机理。结果显示：心内膜垫形成之前，心内膜细胞基底面呈层粘连蛋白和纤维粘连蛋白阳性，当内膜细胞转化为内膜垫细胞时，其基底面的粘连蛋白和纤维粘连蛋白消失，心胶质和心肌膜中层粘连蛋白，纤维粘连     

妊娠滋养细胞疾病中NF-κBp65和IκBα的表达及临床意义

目的:分析核转录因子κB p65(NF-κBp65)和核转录因子κB抑制蛋白α(IκBα)在正常早孕绒毛及妊娠滋养细胞疾病中表达的差异性,以及与妊娠滋养细胞肿瘤(GTN)(包括侵蚀性葡萄胎和绒毛膜癌)患者年龄及临床分期的关系。并探讨两者在妊娠滋养细胞肿瘤组织中的相关性。方法:采用免疫组化方法(SP法)检测20例正常早孕绒毛组织、30例葡萄胎组织、13例侵蚀性葡萄胎和15例绒毛膜癌中NF-κBp65和IκBα的表达情况。结果:NF-κBp65在正常早孕绒毛组与侵蚀性葡萄胎组、正常早孕绒毛组与绒毛膜癌组、葡萄胎组与侵蚀性葡萄胎组、葡萄胎组与绒毛膜癌组之间阳性表达率比较差异均具有统计学意义(P=0.013,0.018,P=0.026,0.035,P<0.05);IκBα在正常早孕绒毛组与侵蚀性葡萄胎组、正常早孕绒毛组与绒毛膜癌组、葡萄胎组与侵蚀性葡萄胎组、葡萄胎组与绒毛膜癌组之间阳性表达率比较差异均具有统计学意义(P<0.01)。NF-κBp65和IκBα在GTN中的表达与临床分期有关(P=0.043,0.042,P<0.05),与患者年龄无关。NF-κBp65与IκBα在GTN中呈负相关(r=-0.403,P=0.034,P<0.05)。结论:NF-κBp65上调、IκBα的下降或缺失可能与滋养细胞肿瘤的发生发展以及侵袭、转移有关,NF-κBp65、IκBα两者在妊娠滋养细胞肿瘤组织中的表达呈负相关。     

层粘连蛋白和纤维粘连蛋白在过量维生素A酸致心脏畸形中的作用:免疫组织化学研究

维生素A酸是常见的一类化学致畸因子,可引起各种心脏畸形,如主动脉骑跨、室间隔缺损等.实验采用免疫组织化学方法观察层粘连蛋白和纤维粘连蛋白在心脏正常和异常发育过程中的分布和变化规律,以探讨过量维生素A酸致心脏畸形发生的机理.结果显示:心内膜垫形成之前,心内膜细胞基底面呈层粘连蛋白和纤维粘连蛋白阳性;当内膜细胞转化为内膜垫细胞时,其基底面的层粘连蛋白和纤维粘连蛋白消失,心胶质和心肌膜中层粘连蛋白、纤维粘连蛋白免疫组化染色明显增强;心内膜垫形成并融合后,其染色又明显减弱.给孕鼠灌服过量的维生素A酸18小时后,各时间组胚胎心脏的心内膜、心胶质、心肌膜的层粘连蛋白和纤维粘连蛋白均出现了不同程度的减弱.这说明层粘连蛋白和纤维粘连蛋白是内膜垫细胞粘着和迁移的主要介导物质,维生素A酸抑制其两者的合成是引起心脏畸形的一个重要途径.     

妊娠滋养细胞病变中FHIT和PTEN蛋白的表达

目的　探讨抑癌基因FHIT、PTEN蛋白表达在妊娠滋养细胞疾病发生、发展中的作用及临床病理意义。方法　采用免疫组化S P法分别检测了 30例完全性葡萄胎、15例侵袭性葡萄胎、15例绒毛膜细胞癌中FHIT、PTEN的蛋白表达。结果　完全性葡萄胎中FHIT蛋白表达低于正常早孕绒毛 (P <0 0 1) ,FHIT蛋白表达与葡萄胎滋养细胞增生呈负相关关系。侵袭性葡萄胎和绒毛膜细胞癌中FHIT蛋白表达均低于完全性葡萄胎 (P <0 0 5 ,P <0 0 1)。侵袭性葡萄胎和绒毛膜细胞癌中核PTEN蛋白表达均低于完全性葡萄胎 (P <0 0 1,P <0 0 1)。绒毛膜细胞癌中核PTEN蛋白表达与临床分期呈负相关关系。结论　FHIT和PTEN蛋白表达下降或缺失可能参与了妊娠滋养细胞疾病的发生、发展过程。     

纤维粘连蛋白在不明原因流产合体滋养细胞中的核定位与凋亡

纤维粘连蛋白存在核内结合区，其功能不甚清楚，文内用免疫组织化学方法对不明原因流产合体滋养细胞纤维粘连蛋白和死亡基因蛋白ｂａｋ进行显微定位研究，结果显示：纤维粘连蛋白在合体滋养细胞核内呈免疫反应用性，ｂａｋ在合体滋养细胞膜呈强阳性着色，提示纤维粘连蛋白在合体滋养细胞的核内结合与不明原因流产的调亡可能相关。     

PCNA和Caspase-3在妊娠滋养细胞疾病中的表达及意义

目的研究PCNA和Caspase-3在妊娠滋养细胞疾病中的表达变化及意义,为妊娠滋养细胞疾病早期诊断、预后判断提供理论依据。方法收集滋养细胞疾病标本50例,其中葡萄胎10例(均为完全性葡萄胎),侵蚀性葡萄胎20例,绒毛膜癌20例。正常早孕绒毛标本10例为对照组。应用免疫组织化学技术检测PCNA和Caspase-3在早孕绒毛、葡萄胎、侵蚀性葡萄胎、绒毛膜癌组织中的表达情况。结果 PCNA在正常早孕绒毛、葡萄胎、侵蚀性葡萄胎和绒癌中的表达分别为10.24%、20.70%、50.92%、53.65%,各组差异有统计学意义(P0.05)。Caspase-3在正常早孕绒毛、葡萄胎、侵蚀性葡萄胎和绒癌中的表达先升高又降低,分别为1.25%、2.60%、6.40%、1.90%,各组差异有统计学意义(P0.05)。结论 PCNA及Caspase-3表达异常,增殖/凋亡失衡是引起GTT的重要因素。     

DEVELOPMENTAL REGULATION OF TISSUE TRANSGLUTAMINASE DURING HUMAN PLACENTATION AND EXPRESSION IN NEOPLASTIC TROPHOBLAST

The expression of tissue transglutaminase (tTG) was studied during the formation of the normal human placenta and in molar pregnancies and choriocarcinoma, in order to correlate its expression with the functional characteristics of the recognized trophoblast cell types. tTG expression was found to be developmentally regulated. Before 6–7 weeks' gestation, only the chorionic villous cytotrophoblast expresses tTG. Thereafter the overlying syncytiotrophoblast becomes positive. tTG expression is gradually downregulated in the intermediate trophoblast cells emerging from the tips of the chorionic villi invading the uterine tissue. In the decidual wall, the intermediate trophoblast does not express tTG, whereas scattered syncytial cells, the placental bed giant cells, express tTG. Villi from complete hydatidiform mole (CHM) show tTG expression in both the cyto- and the syncytiotrophoblast. The intermediate trophoblast cells from CHM show heterogeneous tTG expression, with a majority of negative cells, whereas extravillous syncytia always express tTG. In choriocarcinoma, the tumour cells show heterogeneous tTG expression, with a majority of positive cells. Analysis of tTG protein and mRNA in placental extracts by Western and Northern blotting did not provide evidence for expression of the truncated form of tTG found in some cell types. The regulated expression of tTG in the normal placenta suggests that the enzyme is involved in important trophoblastic functions and may participate in the control of invasion. © 1997 by John Wiley & Sons, Ltd.     

Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease.

AIMS: To study the localisation of the endothelial nitric oxide synthase (eNOS) in the normal placenta, with special emphasis on the implantation site in the first trimester of pregnancy, and in the different subtypes of trophoblastic cells in gestational trophoblastic disease. METHODS: The immunoperoxidase technique with an antibody directed against eNOS was applied to paraffin sections from first and second trimester placentas, placenta accreta, partial and complete hydatidiform moles, and choriocarcinoma. Immunoperoxidase staining for human placental lactogen (hPL) was performed on parallel sections. RESULTS: Prominent immunoreactivity for eNOS was found to be present in the intermediate trophoblastic cells of the cell columns of the anchoring villi and in trophoblastic cells at the implantation site. Staining was also present in the syncytiotrophoblast, most conspicuous at the apical cell border. In trophoblastic disease, proliferating large mononuclear cells, which were strongly positive for hPL, were found to be immunoreactive for eNOS. CONCLUSIONS: eNOS immunoreactivity is strongly positive in the extravillous trophoblastic cells and to a lesser extent in the syncytiotrophoblast. In the former it may play a role in implantation and vascular invasion. Cells with differentiation to intermediate trophoblast in complete hydatidiform mole and choriocarcinoma also show high levels of eNOS, which may be associated with the haematogenous mode of spread of trophoblastic disease.     

Telomerase activity in gestational trophoblastic disease

AIMS: To investigate the pattern of telomerase activity in hydatidiform mole as compared with normal placenta and choriocarcinoma, and to determine the prognostic significance of telomerase activity in hydatidiform mole. METHODS: Telomerase activity in 35 cases of hydatidiform mole, 35 normal placentas, one choriocarcinoma sample, and two choriocarcinoma cell lines (JAR, JEG3) was determined using the sensitive polymerase chain reaction based telomeric repeat amplification protocol (TRAP) assay. Two cases of breast carcinoma and two cases of ovarian carcinoma were also included as positive controls in the telomerase assay. RESULTS: Telomerase activity was detected in 11 of 30 early placentas (36.7%), one of five term placentas (20%), five of 27 hydatidiform moles which regressed spontaneously (18.5%), and six of eight hydatidiform moles which developed persistent trophoblastic disease (75%) (including three which developed metastases). Hydatidiform moles which subsequently developed persistent disease, especially those which metastasised, were more likely to express telomerase activity (p < 0.01). However, there was no significant difference in the frequency of telomerase activity between early placentas and hydatidiform mole. Strong telomerase activity was observed in choriocarcinoma tissue, choriocarcinoma cell lines, and ovarian and breast carcinomas. CONCLUSIONS: Telomerase activation occurs in hydatidiform mole with a similar incidence to early normal placentas. This supports the concept that hydatidiform mole is essentially an abnormal conceptus. There is an association between telomerase activation and the development of persistent trophoblastic disease. Further study is warrant to confirm the prognostic significance of telomerase activity in hydatidiform mole.     

P57kip2 immunohistochemical expression and ultrastructural findings of gestational trophoblastic disease and related disorders

Gestational trophoblastic disease (GTD) is a unique spectrum of diseases ranging from complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and invasive mole (IM) to choriocarcinoma (CC). Placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) have been classified as related disorders. Mesenchymal dysplasia (MD) may be misdiagnosed as PHM; however, it is said to have a quite different histogenesis from PHM. P57kip2 is the protein product of a paternally imprinted or maternal gene that inhibits cyclin-dependent kinases (CDK), thus serving to inhibit cell proliferation and to suppress tumor growth. Its lack of expression in trophoblastic disease plays a role in its abnormal proliferation and differentiation. In this study, P57kip2 immunostaining was absent in the trophoblastic layers of CHM and was positive in the trophoblast layer of nonmolar villi and MD. Ultrastructure of complete molar cystic villi showed tree-like branching of microvillous processes and intracytoplasmic lacunae without capillaries in the stroma, whereas MD contained many newly formed blood vessels and collagen. Also, large lacunae with microvilli and polymorphic nuclei of syncytiotrophoblast cells with well-developed organelles were observed in IM. Lung ETT following CHM and normal deliveries showed two types of large mononuclear cells and binuclear cells with abundant organelles and bundles of intermediate-type filaments in the stroma.     

滋养细胞肿瘤DNA图像定量分析

目的:探讨图像分析技术对滋养细胞肿瘤DNA定量分析的应用价值.方法:应用图像分析技术对33例滋养细胞肿瘤细胞核DNA含量进行了定量测定和比较.结果:从正常绒毛→良性葡萄胎→恶性葡萄胎→绒毛膜癌:DNA含量和非整倍体细胞呈增高趋势.恶性葡萄胎和绒毛膜癌明显高于良性葡萄胎和正常绒毛,有显著性差异(P<0.01).良性葡萄胎高于正常绒毛,但两者相比无显著性差异(P>0.05).绒毛膜癌高于恶性葡萄胎,但两者相比亦无显著性差异(P>0.05).结论:图像分析仪对滋养细胞肿瘤DNA定量分析,可对该肿瘤的诊断、化疗、预后提供重要信息.     

Trophoblastic tumor at the site of the placenta

The author describes the histological structure of a rare placental site trophoblastic tumor. In differential diagnosis it is necessary to take into account hydatidiform mole and chorionepithelioma. In differentiating with hydatidiform mole lack of placental villi is characteristic while with choriocarcinoma the presence of connective stroma in PSTT is helpful.     

Invasive hydatiform mole in a postmenopausal woman

Gestational trophoblastic disease occurs rarely in postmenopausal women. We report the case of a 51 year-old postmenopausal woman with an invasive complete mole. Invasive mole should be distinguished from choriocarcinoma, by a thorough sampling showing infiltrative molar villi associated with a prominent trophoblastic proliferation. Gestational trophoblastic diseases in postmenopausal women can represent malignant changes of trophoblastic remnants of a prior pregnancy after a period of latency or correspond to a possible current pregnancy as demonstrated by an ovarian corpus luteum of pregnancy in our patient. The unusual finding in our case is that the gestational trophoblastic disease follows a pregnancy occurring after a biologically confirmed menopause.     

层粘连蛋白和纤维粘连蛋白在着床期小鼠子宫内膜中的表达

目的：为探讨层粘连蛋白和纤维粘连蛋白在胚泡着床过程中的生物学作用。方法：本实验使用昆明雌性小鼠30只,分为未孕和早期妊娠共6组。通过免疫组织化学方法,检测了层粘连蛋白和纤维粘连蛋白在着床期小鼠子宫内膜中的分布状况。结果：胚泡着床开始时（即受精后4－5天）,层粘连蛋白和纤维粘连蛋白均出现一个表达高峰,尔后纤维粘连蛋白迅速减少。受精后6－8天,细胞外基质中的层粘连蛋白逐渐增加。结论：层粘连蛋白和纤维粘连蛋白在胚泡着床微环境和植入调节中发挥重要作用。     

Alterations of basement membrane in di-isopropanolnitrosamine- induced carcinogenesis of the rat thyroid gland: an immunohistochemical study

Alterations of basement membrane (BM) in di-isopropanolnitrosamine (DIPN)-induced carcinogenesis of the rat thyroid gland were examined by means of immunohistochemical localization of collagen type IV (CN-IV), laminin (LN), and fibronectin (FN) in pre-nodular and nodular thyroid lesions, correlating with the morphogenesis and proliferative activity of these lesions. Adult male rats of the Wistar strain were injected s.c. in the back with DIPN, and the thyroid glands were removed at the 15th and 30th week of treatment. Each of 133 thyroid lesions was histochemically analyzed. The follicular epithelial BM as revealed by CN-IV and LN was discontinued or completely lost during the progression of thyroid lesions from pre-nodular to nodular lesions and finally overt carcinomas. At the same time, the BM of vascular endothelial cells demonstrated a loss of dense capillary networks of follicles, a sinusoidal dilatation and, predominantly in carcinomas, development of interstitial-type blood vessels. However, FN, which was hardly stained in the normal thyroid tissue, was remarkably deposited in the interstitium of invasive carcinomas. These observations strongly suggested that alterations of BM structure play a key role in the morphogenesis of rat thyroid tumors, and that the expression of FN is an important step in the invasive growth of thyroid tumors. Received: 12 October 1999 / Accepted: 30 December 1999