不同滋养细胞在恶性滋养细胞肿瘤中的分布

 应用免疫组化方法,采用抗细胞角蛋白(CK)、绒毛膜促性腺激素(hCG)、胎盘泌乳素(hPL)抗体,检测了91例恶性滋养细胞肿瘤不同类型滋养细胞的分布情况.结果显示,侵袭性葡萄胎和绒毛膜癌的滋养细胞组成不同.二者除了均具有较多合体滋养细胞(ST)外,前者中间型滋养细胞(IT)数量较后者明显增多,而后者细胞滋养细胞(CT)则较前者明显增多.转移性侵袭性葡萄胎与原发瘤在滋养细胞组成上无显著差异,但转移性绒毛膜癌ST较原发瘤明显增多,CT较原发瘤显著减少,IT数量虽有一定增加,但与原发瘤无显著差异.作者认为,合体滋养细胞在恶性滋养细胞肿瘤中的作用尚须进一步探讨.     

纤溶酶原激活剂在妊娠滋养细胞疾病中的表达及其与肿瘤侵袭的关系

目的:明确尿激酶型纤溶酶原激活剂(uPA)在妊娠滋养细胞肿瘤中的表达及其与恶性滋养细胞肿瘤侵袭的关系。方法:应用分子原位杂交技术检测葡萄胎、侵蚀性葡萄胎及绒毛膜癌标本中uPA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:①uPA在葡萄胎、侵蚀性葡萄胎及绒毛膜癌中的表达差异有显著性(P<0.001);②通过秩和检验对各组进行两两比较,uPA在侵蚀性葡萄胎及绒毛膜癌中的表达比葡萄胎均显著增高(P<0.001)。③侵蚀性葡萄胎及绒毛膜癌浸润子宫肌层的深度与uPA的表达状况差异有显著性(P<0.05)。结论:滋养细胞的恶性生物学行为与uPA的表达异常之间存在着一定的相关性。     

nm23基因在恶性滋养细胞肿瘤中的表达及其意义

 目的　研究nm2 3基因在恶性滋养细胞肿瘤中的表达和意义。方法　采用LSAB免疫组化染色方法 ,检测nm2 3基因在 91例恶性滋养细胞肿瘤中的表达水平。结果　nm2 3在侵袭性葡萄胎的阳性表达率 ( 10 0 % )显著高于绒毛膜癌 ( 68 63% ) (P <0 0 1)。在不同肿瘤性滋养细胞中 ,合体滋养细胞 (ST)基本不表达 ,中间型滋养细胞 (IT)和细胞滋养细胞 (CT)部分表达 ,但侵袭性葡萄胎中IT阳性表达率 ( 62 50 % )极明显高于绒毛膜癌 ( 3 92 % ) (P <0 0 1)。侵袭性葡萄胎原发瘤强阳性表达率 ( 82 76% )明显高于转移瘤 ( 2 7 2 7% ) ,原发性绒毛膜癌阳性表达率 ( 84 37% )明显高于转移性绒毛膜癌 ( 4 2 11% ) ,差异均具有高度显著性 (P <0 0 1)。结论　nm2 3基因的表达水平与恶性滋养细胞肿瘤的分化呈正相关 ,与肿瘤的转移能力呈负相关     

E-cadherin及nm23-H1在滋养细胞疾病中的表达及意义

目的:探讨E-cadherin及nm23-H1基因在妊娠滋养细胞疾病发生发展中的作用.方法:采用免疫组化法检测24例葡萄胎(随访2年以上未发生恶变)、15例侵蚀性葡萄胎、15例绒毛膜上皮癌、18例正常绒毛组织的石蜡包埋标本E-cadherin和nm23-H1基因的表达状况.结果:E-cadherin的表达在正常早孕绒毛高于侵蚀性葡萄胎和绒毛膜癌(P＜0.01),葡萄胎高于侵蚀性葡萄胎和绒毛膜癌(P＜0.05).nm23-H1的表达正常早孕绒毛明显高于恶性滋养细胞疾病(P＜0.01),葡萄胎高于侵蚀性葡萄胎(P＜0.01)和绒毛膜癌(P＜0.05).在葡萄胎和恶性滋养细胞疾病中E-cadherin和nm23-H1基因的表达均为正相关.结论:滋养细胞疾病E-cadherin和nm23-H1表达与其侵袭性相关,二者可能成为葡萄胎预后的标志物.在侵袭转移过程中细胞滋养细胞较合体滋养细胞更为重要.     

基质金属蛋白酶-2在妊娠滋养细胞疾病中的表达及意义

目的:探讨基质金属蛋白酶-2(m atrix m etalloprote inase,MMP-2)在妊娠滋养细胞疾病中的表达。方法:应用免疫组化SP法检测正常早孕妇女胎盘绒毛10例、葡萄胎20例、侵蚀性葡萄胎32例及绒毛膜癌16例组织中MMP-2的表达情况。结果:MMP-2主要表达于合体滋养细胞、绒毛外滋养细胞。正常早孕绒毛组织、妊娠滋养细胞疾病组织中,MMP-2均有阳性表达,早孕绒毛与早孕期葡萄胎间有显著差异(P<0.05),与葡萄胎病理分型、胎次无相关性,早孕期葡萄胎MMP-2阳性表达率显著高于晚孕期葡萄胎(P<0.05)。正常绒毛组MMP-2阳性表达率与葡萄胎组、侵蚀性葡萄胎组和绒毛膜癌组相比有显著性差异(P<0.05)且有逐渐上升趋势,但其余各组间无统计学意义。MMP-2表达与侵蚀性葡萄胎、绒毛膜癌临床分期无相关性。侵蚀性葡萄胎组中未化疗者MMP-2阳性表达率显著高于化疗者(P<0.05);绒毛膜癌组中未化疗组MMP-2阳性表达率高于化疗组,但无统计学意义。结论:MMP-2与滋养细胞的浸润活性呈正相关,与孕周呈负相关,可能与正常滋养细胞浸润行为的时空阶段性和限制性有关。随着妊娠滋养细胞疾病恶性程度升高MMP-2逐渐呈强表达,化疗后其阳性表达明显下降,提示MMP-2可能作为临床早期诊断妊娠滋养细胞疾病、判断治疗疗效及预后的重要指标之一。     

表皮生长因子受体及nm23-H1在滋养细胞肿瘤中表达的相关性及临床意义

葡萄胎、侵蚀性葡萄胎和绒毛膜癌是发生在育龄期妇女中较常见的滋养细胞肿瘤。我们采用免疫组化方法 ,检测表皮生长因子受体 (ｅｐｉｄｅｒｍａｌｇｒｏｗｔｈｆａｃｔｏｒｒｅｃｅｐｔｏｒ,ＥＧＦＲ)及ｎｍ2 3 Ｈ1基因在正常早孕绒毛和滋养细胞肿瘤组织中的蛋白表达量 ,以探讨其与滋养细胞肿瘤的关系 ,特别是对葡萄胎恶性变的预测价值进行了分析。一、材料与方法1 标本来源 :恶性滋养细胞肿瘤 18例 (侵蚀性葡萄胎10例、绒毛膜癌 8例 )为北京协和医院 1986年 8月～ 1999年3月急症手术切除的子宫标本。葡萄胎为同期收治的部分患者 ,共 2 0例 …     

高危型绒癌3例和侵蚀性葡萄胎1例报道

0引言妊娠滋养细胞肿瘤(gestational trophoblastic neoplasia,GTN)是来源于胎盘滋养细胞的一组少见的恶性疾病。根据国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)2018最新分类,GTN在组织学上包括侵蚀性葡萄胎、绒毛膜癌(绒癌)、胎盘部位滋养细胞肿瘤、上皮样滋养细胞肿瘤和非典型胎盘部位结节[1]。     

VE-cadherin在妊娠滋养细胞疾病的表达及其临床意义初步探讨

目的:探讨VE-cadherin在妊娠滋养细胞疾病的表达及其临床价值.方法:采用逆转录聚合酶链反应技术,检测22例正常早孕绒毛和非恶变葡萄胎23例,恶变葡萄胎12例,侵蚀性葡萄胎11例和绒毛膜癌9例共55例妊娠滋养细胞疾病组织中VE-cadherin mRNA的表达量.结果:VE-cadherin mRNA在正常早孕绒毛与非恶变葡萄胎组织的表达量的差异无统计学意义(P＞0.05);恶变葡萄胎、侵蚀性葡萄胎和绒癌的表达量明显低于正常早孕绒毛和非恶变葡萄胎;侵蚀性葡萄胎和绒癌的表达量低于恶变葡萄胎;绒癌的表达量低于侵蚀性葡萄胎(P＜0.01).结论:VE-cadherin mRNA的表达下调可能是滋养细胞恶性转化的早期事件,与葡萄胎的恶变有关.检测VE-cadherin的表达可望成为预测葡萄胎恶变以及妊娠滋养细胞肿瘤(GTT)预后评价的参考指标.     

不同妊娠滋养细胞疾病组织中RFC2、PCNA表达的研究

背景与目的：基因表达谱芯片检测发现葡萄胎和绒毛膜癌存在复制因子C(replication factor C,RFC)高表达。复制因子C亚单位2(replication factor C subunit2,RFC2)与DNA的复制和修复及细胞周期信号检查点的功能有关。本研究检测RFC2和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)蛋白在妊娠滋养细胞疾病(gestational trophoblastic disease,GTD)中的表达情况,探讨二者表达的意义。方法：采用免疫组化SP法检测15例正常绒毛、38例葡萄胎、42例侵蚀性葡萄胎和18例绒毛膜癌组织中RFC2和PCNA蛋白表达情况。结果：葡萄胎、侵蚀性葡萄胎、绒毛膜癌组织中的RFC2和PCNA蛋白表达水平显著高于正常绒毛(PRFC2=0．000,PPCSA=0．004)。葡萄胎、侵蚀性葡萄胎、绒毛膜癌组织中RFC2的表达水平无显著性差异(P值分别为1．000、0．256)。术前未化疗的滋养细胞肿瘤患者(包括侵蚀性葡萄胎和绒毛膜癌)的RFC2表达高于术前化疗≥3疗程者(P=0．028)。WHOⅢ期者RFC2蛋白表达高于I期者(P=0．01)。WHO预后评分为高危者,其RFC2表达显著高于低危者(P=0．018)。绒毛膜癌组织中PCNA的表达高于葡萄胎(P=0．037),葡萄胎恶变者PCNA的表达高于未恶变者(P=0．039)。高危组、中危组PCNA的表达高于低危组(P=0．036,P=0．048)。PCNA的表达与滋养细胞肿瘤术前是否化疗、WHO分期无关。PCNA与RFC2的表达呈正相关(spearman相关系数为0．514,P=0．000)。结论：RFC及PCNA的过度表达可能与滋养细胞肿瘤的生物学行为有关。     

葡萄胎恶变的研究

葡萄胎分完全性和部分性两种,系妊娠滋养细胞疾病中最多者,但它有部分会恶变为侵蚀性葡萄胎或绒毛膜癌(简称绒癌),也有少数恶变成胎盘部位滋养细胞肿瘤.     

妊娠性滋养细胞肿瘤P185和雌孕激素受体的表达及意义

以ＡＢＣ法检测了４０例妊娠性滋养细胞肿瘤石蜡标本Ｐ１８５及ＥＲ、ＰＲ的表达。其中绒毛膜癌２４例。侵蚀性葡萄胎１６例，Ｐ１８５阳性率为４０％，ＥＲ、ＰＲ阳性率分别为４５％，７５％，Ｐ１８５在侵蚀性葡萄胎中的阳性率均明显高于绒瘤（Ｐ＜０．０１）。病程小于１年者，Ｐ１８５的阳性率高于病程大于１年者（Ｐ＜０．０５），ＥＲ、ＰＲ阳性者，Ｐ１８５的阳性率分别高于其阴性者（Ｐ＜０．０５、Ｐ＜０．０１），Ｐ１８５阳性与阴性的患者，分别有８１．３％、５０％的患者于３疗程内血ｈＣＧ转阴（Ｐ＜０．０５）。资料提示：Ｐ１８５倾向于在滋养细胞肿瘤恶性转化的早期表达，Ｐ１８Ｓ阳性者对化疗较为敏感。     

Trophoblastic proteins as tumor markers in nonseminomatous germ cell tumors

In order to examine the relative usefulness of measurements of oncoplacental proteins as tumor markers in patients with nonseminomatous germ cell tumors, the authors measured alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), pregnancy-specific beta 1-glycoprotein (SP1), human placental lactogen (hPL), and placental cystine aminopeptidase (oxytocinase, CAP) in serial blood samples obtained from 26 men with these neoplasms. HCG and AFP were each elevated in 62% of the patients and both were elevated in 38%. SP1 and hPL were increased in 31% and 12%, respectively. None of the patients had elevated CAP activity. Serum hCG and SP1 concentrations were strongly correlated (r = 0.78, P less than 0.001). No patient had an elevated SP1 without a concomitant elevation in serum hCG. Serial measurements of hCG and SP1 indicated that they were concordant in five of the eight patients in whom both were elevated, and AFP and hCG were concordant in only one half of the ten patients in whom both markers were elevated. The number of patients with hPL elevations were too few for meaningful comparison of this marker with the others. These results indicate that measurements of SP1, hPL, and CAP do not provide additional useful information over that obtained from measurements of hCG and AFP in patients with nonseminomatous germ cell tumors.     

Lack of mutation in tumour-suppressor gene p53 in gestational trophoblastic tumours.

The objectives of this study were to better our understanding of the carcinogenesis of gestational trophoblastic tumours and to investigate the possible presence of mutational alteration of the p53 tumour-suppressor gene in these tumours. Amplification-based direct DNA sequencing was performed on 14 hydatidiform moles, six invasive moles, eight choriocarcinomas and ten normal early placental tissues. No mutation in exons 5-8 was detected in any of these 38 tissue specimens. These results suggest that a mutation in p53 tumour suppressor either does not exist or is a very rare event in gestational trophoblastic tumours. The gestational trophoblastic tumours probably involve a tumour-suppressor gene other than p53 gene or may follow a completely different pathway to their malignant phenotype.     

Immunohistochemistry of germ cell and trophoblastic neoplasms

The immunoprofiles of 121 germ cell and trophoblastic neoplasms were defined, using a battery of antibodies against cytokeratin (CK), vimentin (VIM), epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), S-100 protein, leukocyte common antigen (LCA), UCHL-1, LN-2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), chromogranin A, Leu-7, alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), and the beta subunit of human chorionic gonadotropin (BHCG). In addition to 85 neoplasms of testicular origin, the cases included eight ovarian germ cell tumors and 28 extragonadal neoplasms. All tissues had been subjected to formalin fixation and paraffin embedding. Similar immunoreactivity patterns were seen in gonadal and extragonadal neoplasms, gestational and nongestational choriocarcinomas, components of mixed germ cell tumors and their pure counterparts, and metastatic and primary lesions. Placental alkaline phosphatase was a sensitive marker of germ cell differentiation, and expression of this marker in the absence of EMA appeared to be a staining pattern unique to germ cell tumors. Both LCA and S100 were absent in neoplastic germ cells, and thus were useful in differentiating these tumors from malignant lymphoma and malignant melanoma, respectively. Cytokeratin was helpful in distinguishing seminomas/dysgerminomas from nonseminomatous germ cell tumors, although 10% of seminomas showed focal or diffuse cytokeratin reactivity. Finally, 75% of all germ cell neoplasms displayed NSE, calling the specificity of this determinant into question.     

Expression of cyclin E in placentas with hydropic change and gestational trophoblastic diseases: implications for the malignant transformation of trophoblasts

BACKGROUND: Although much is known about the morphologic, cytogenetic, and clinical characters of gestational trophoblastic diseases, little information has appeared concerning the parameters related to their persistence or neoplastic transformation. Cell cycle alterations in tumor tissue were examined in this study in light of obvious changes in the clinical behavior of malignant cells. There is an increasing body of evidence suggesting that the abnormal expression of cyclins is considered one of the most important events in malignant transformation of various human cancers. Among these cell cycle regulators, the role of cyclin E in the neoplastic transformation of trophoblast populations has been poorly defined. METHODS: Using formalin fixed, paraffin embedded trophoblastic tissues, the authors investigated the expression of cyclin E by immunohistochemistry in placentas with hydropic change and gestational trophoblastic diseases. The specimens examined included tissue from 29 patients with complete hydatidiform mole, 18 patients with partial hydatidiform mole, and 6 patients with choriocarcinoma after term pregnancy or abortion. The authors also studied four cases of hydropic abortion. RESULTS: The cyclin E indexes (CEI) were as follows: 25.7% +/- 6.2% for hydropic change, 35.3% +/- 12.7% for triploid partial moles, 42.2% +/- 13.1% for diploid/tetraploid complete moles, and 63.6% +/- 9.5% for choriocarcinomas. There was a significant difference in CEI between placentas with hydropic change and partial mole (P = 0.04) and placentas with hydropic change and complete mole (P = 0.003). Choriocarcinomas had significantly higher cyclin E expression compared with placentas, partial moles, and complete moles, respectively. A significant correlation between the expression of cyclin E and S-phase fraction was observed in gestational trophoblastic diseases (rank correlation coefficient = 0.45, P < 0. 05). The relation between cyclin E expression and proliferation was abrogated in placentas with hydropic change, suggesting that cyclin E up-regulation represents a genuine aberration. CONCLUSIONS: The results of this study were consistent with the concept that cyclin E overaccumulation may play an important role in the uncontrolled proliferation and neoplastic transformation of trophoblasts.     

Circulating levels and tissue localization of placental protein five (PP5) in pregnancy and tropho-blastic disease: Absence of PP5 expression in the malignant trophoblast

Placental protein five (PP5) was studied by radio-immunoassay in 360 serum samples from 334 pregnant women, 96 serum samples from eight patients with trophoblastic disease, and 80 samples from apparently healthy women. PP5 was not found in the serum of healthy controls. It became detectable in maternal serum 8 weeks after the last menstrual period, and the levels progressively increased as pregnancy advanced. The highest levels (mean 26–29 ng/ml) were seen between weeks 37–39 of gestation. PP5 was rarely found in the serum of patients with trophoblastic disease. The first pretreatment samples of two patients with hydatidiform mole had PP5 levels of 0.6 and 2 ng/ml when the concentrations of human chorionic gonadotrophin (hCG) and pregnancy-specific beta-1-glycoprotein (PSBG) were high, whereas the subsequent 17 samples were PP5-negative. All seven samples from a patient with invasive mole and 70 samples from five patients with choriocarcinoma were PP5-negative including those with high hCG and PSBG concentrations. Even a patient whose choriocarcinoma followed term pregnancy had no detectable PP5 in the serum. The occurrence of PP5 in tissue was studied by the three-layer bridge immunoperoxidase method. PP5 was localized in the syncytiotrophoblast between 6 and 42 weeks of gestation, but the cytotrophoblast was PP5-negative. The staining for PP5 was positive in all hydatidiform moles tested and in one of 10 cases of invasive mole. Choriocarcinomas were constantly PP5-negative (6 cases). In the light of the biological role of PP5 as trypsin and plasmin inactivator its presence in normal and absence from malignant trophoblast suggests that PP5 may be involved in the regulation of trophoblastic invasiveness. The absence of PP5 expression in malignant trophoblastic disease makes it possible to use the serum PP5 measurement for the differential diagnosis of trophoblastic disease and normal pregnancy: in normal pregnancy the placental proteins PP5, hCG and PSBG are all present in serum 10 weeks after the last menstrual period, whereas in malignant trophoblastic disease hCG and PSBG are expressed in the absence of PP5.     

胎盘部位滋养细胞肿瘤临床病理分析

目的:分析胎盘部位滋养细胞肿瘤(PSTT)的临床及病理特点,探讨其形态与预后的关系。方法:对4例PSTT进行临床、光镜及免疫组化研究。结果:PSTT一般发生于育龄妇女,临床常见症状为阴道出血。4例中前次妊娠人工流产1例,引产1例,足月分娩2例。光镜下均以种植部位中间型滋养细胞为主,在子宫肌壁间浸润性生长,并伴有特征性的血管浸润,免疫组化表现为胎盘泌乳素（hPL）弥漫阳性,绒毛膜促性腺激素（hCG）局灶阳性或阴性。结论:PSTT是一种罕见肿瘤,由种植部位中间型滋养细胞构成,呈惰性的生物学行为,预后较好。     

Human chorionic gonadotropin and human placental lactogen in extragonadal tumors. An immunoperoxidase study of ten non-germ cell neoplasms

The immunoperoxidase localization of the alpha and beta subunits of human chorionic gonadotropin (hCG) and of human placental lactogen (hPL) was studied in ten extragonadal nontrophoblastic tumors associated with raised serum levels of one or more of these placental proteins. Three of the tumors were bronchial carcinomas, one was a gastric carcinoma, two were malignant carcinoids (one bronchial and one gastric), two were pancreatic islet cell carcinomas, and two were metastatic carcinomas with an unknown primary site. The maximum alpha subunit serum level was 33,000 ng/ml (gastric carcinoid), the maximum hCG/hCG-beta level was 705,000 ng/ml, and the maximum hPL level was 50 ng/ml (both in the gastric carcinoma). An indirect immunoperoxidase technique and rabbit polyclonal affinity-purified antibodies and peroxidase conjugates were used on formalin-fixed, paraffin-embedded sections. Five blocks (eight cases) or six blocks (two cases) from various sites were obtained from each patient at surgery and/or autopsy. Positive stains for hCG/hCG-beta were seen in six of seven tumors (25/37 blocks) with raised levels, for the alpha subunit in nine of nine tumors (30/47 blocks), and for hPL in two of five tumors (4/26 blocks). Only a relatively minor number of the cells were positive, and within the same case, there was considerable site-to-site variation in the number of positive cells. Large bizarre cells contained hCG/hCG-beta as well as the alpha subunit, if it was demonstrated in the same tumor as the beta subunit. Otherwise, the alpha subunit was found in small unremarkable cells. Giant cells that were smaller than those positive for hCG/hCG-beta contained in hPL. In some serial sections, hCG-alpha, hCG/hCG-beta, and hPL were segregated in different cell populations, supporting the concepts of their separate genetic control.     

滋养细胞肿瘤核仁蛋白组成区研究

 运用核仁蛋白组成区嗜银蛋白染色术检测了5例正常胎盘,1例合体细胞子宫内膜炎,22例葡萄胎,10例恶性葡萄胎,2例胎盘部位中间型滋养细胞肿瘤和19例绒癌,发现恶性滋养细胞肿瘤的AgNOR/核均数明显高于良性滋养细胞肿瘤(P<0.001),细胞滋养细胞中的AgNOR/核均数亦明显高于合体滋养细胞(P<0.001).同时发现良恶性滋养细胞肿瘤的AgNOR颗粒分布类型也不同,良性病变以弥漫型为主,而恶性病变以颗粒型为主,表明主要用于细胞遗传学的AgNOR技术在肿瘤病理学上有广泛的应用价值.