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。     

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。     

妊娠滋养细胞肿瘤（疾病）保留生育功能的治疗

妊娠滋养细胞疾病是一系列的疾病，包括葡萄胎、侵蚀性葡萄胎（简称侵葡）、绒毛膜癌（简称绒癌）和胎盘部位滋养细胞肿瘤（简称ＰＳＴＴ）。除葡萄胎外，后三者又统称妊娠滋养细胞肿瘤。葡萄胎约有１４．５％～２０％可恶变为滋养细胞肿瘤，这类疾病大多发生在生育年龄的...     

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.     

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。     

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—cadherinmRNA的表达量。结果：VE—cadherinmRNA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—cadherinmRNA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。     

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.     

恶性滋养细胞肿瘤解剖分期和预后评分的临床意义

目的回顾性分析评价FIGO解剖分期和预后评分在GTT治疗中的临床意义。方法选择有比较完整临床资料的已治GTT患者90例,根据2000年FIGO分期和评分标准,进行解剖分期和预后评分,并据此比较治疗的效果。结果绒癌组高危比例37.8%,侵蚀性葡萄胎组高危比例17.3%。解剖分期为Ⅰ期和Ⅲ期的低危组患者疗效好于同期高危组患者(P<0.05)。在复发的6例患者中,1例为低危,5例属高危者。给予综合治疗的17例疗效满意。结论绒癌患者存在高危因素者多于侵蚀性葡萄胎。在同期别中,低危患者疗效要好于高危者。治疗时应同时参考解剖分期和预后评分并有效利用综合治疗。     

MMP-7和MMP-9在妊娠滋养细胞疾病中的表达

[目的]探讨基质金属蛋白酶-7、9（MMP-7、MMP-9）在妊娠滋养细胞疾病中的表达水平。[方法]采用免疫组织化学PV-6000法测定49例葡萄胎（其中8例发生恶变,列为葡萄胎恶变组）,8例恶性滋养细胞肿瘤（其中6例侵蚀性葡萄胎,2例绒毛膜癌）和18例正常早孕绒毛组织MMP-7、MMP-9的蛋白表达量：用RT—PCR法测定其中的35例葡萄胎（其中6例发生恶变,列为葡萄胎恶变组）和18例正常早孕绒毛组织的MMP-7、MMP．9mRNA表达量。[结果]MMP-7、MMP-9的蛋白表达量在恶性滋养细胞肿瘤及葡萄胎恶变组中的表达分别高于正常绒毛和葡萄胎未恶变组（P〈0．05）;MMP-7、MMP-9mRNA表达量在三组中的表达无显著性差异（P〉0．05）。[结论]MMP．7和MMP．9可能通过降解细胞外基质参与妊娠滋养细胞疾病的发生和发展。     

KiSS-1基因和基质金属蛋白酶-9在妊娠滋养细胞疾病组织中的表达及其意义

目的探讨浸润相关基因KiSS-1和基质金属蛋白酶-9(matrix metalloproteinase,MMP-9)在妊娠滋养细胞疾病中的表达。方法用RT-PCR和Western blot法检测30例正常早期妊娠绒毛、30例葡萄胎、9例侵蚀性葡萄胎和8例绒毛膜癌中KiSS-1和MMP-9mRNA及其蛋白的表达。结果正常妊娠早期绒毛、葡萄胎和侵蚀性葡萄胎组织中均有MMP-9和KiSS-1表达,而在绒毛膜癌组织中仅有MMP-9基因和蛋白的表达,无KiSS-1基因和其蛋白肽metas-tin的表达。妊娠滋养细胞疾病组织[包括葡萄胎、侵蚀性葡萄胎及绒毛膜癌]中MMP-9的基因和蛋白表达均显著高于早期妊娠绒毛组织(P=0·039、0·001、0·000),其中侵蚀性葡萄胎及绒毛膜癌组织中显著高于葡萄胎(P=0·000),绒毛膜癌中MMP-9基因表达水平最高(分别为0·705±0·141和78·403±7·124)。而KiSS-1基因的表达正相反葡萄胎组织的KiSS-1mRNA(0·433±0·193)和metastin表达(23·831±7·522)显著低于早期妊娠绒毛组织(P=0·049、0·049),侵蚀性葡萄胎组织中KiSS-1mRNA和metastin表达水平更低(分别为0·113±0·121和10·814±3·431)。结论促浸润基因MMP-9的表达变化与滋养细胞浸润活性呈正相关,而抑浸润基因KiSS-1的表达变化则与滋养细胞浸润活性呈负相关。这两种基因相互作用在滋养细胞浸润活性调控中起重要作用。     

Gestational trophoblastic tumors

Gestational trophoblastic tumor is a term applied to invasive mole, choriocarcinoma, and placental-site trophoblastic tumor. The overall cure rate in the treatment of these gestational trophoblastic tumors now exceeds 90%. This high success rate is the result of (1) inherent sensitivity of trophoblastic tumors to chemotherapy, (2) ability to monitor therapy effectively with the use of human chorionic gonadotropin as a tumor marker, and (3) identification of prognostic factors which allows categorization of patients into high- and low-risk groups for selection of treatment. Virtually all patients with nonmetastatic and low-risk metastatic disease can be cured using single-agent methotrexate or Actinomycin-D chemotherapy. Intensive therapy with combination chemotherapy including etoposide, high-dose methotrexate and Actinomycin D and, where indicated, adjuvant radiotherapy and surgery has resulted in cure rates of 80-90% in patients with high-risk metastatic disease. The factors which are most important in determining response to treatment are: (1) clinicopathologic diagnosis of choriocarcinoma, (2) metastases to sites other than the lung or vagina, (3) number of metastases, (4) previous failed chemotherapy, and (5) WHO score greater than or equal to 8.     

Treatment of gestational trophoblastic tumors

Opinion statement Gestational trophoblastic tumors (invasive mole, choriocarcinoma, and placental site trophoblastic tumor) should be classified according to the National Cancer Institute (NCI), World Health Organization (WHO), and International Federation of Gynecology and Obstetrics (FIGO) criteria into nonmetastatic, low-risk metastatic, and high-risk metastatic categories. Nonmetastatic tumors (FIGO Stage I) can be treated with a variety of single-agent methotrexate or actinomycin D protocols, resulting in cure of essentially all patients. Metastatic low-risk tumors (FIGO Stages II and III, WHO score < 8) should be treated with 5-day dosage schedules of methotrexate or actinomycin D, with cure rates approaching 100%. Metastatic high-risk tumors (FIGO Stage IV, WHO score > 7) require combination chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) with or without adjuvant radiation therapy and surgery to achieve cure rates of 80% to 90%.     

图像分析检测滋养细胞瘤嗜银蛋白的临床意义

本文选取妊娠滋养细胞肿瘤石蜡包埋的组织块100例，共分5组：（1）正常绒毛（对照组）20例；（2）葡萄胎未恶变组40例；（3）葡萄胎恶变组40例；（4）恶性葡萄胎10例；（5）绒毛膜癌组10例。上述组织切片先按Ploton’s法行核仁组成区银染。再用图像分析法行核仁组成区嗜银蛋白颗粒计数和面积测量，两者结果均显示：组2高于组1（P＜0．001），组3高于组2（P＜0．001），组4高于组3（P＜0．05），组4和组5间无显著差异（P＞0．05），提示图像分析法检测滋养细胞肿瘤嗜银蛋白对预测葡萄胎恶变有一定意义。     

Successful treatment of malignant trophoblastic diseases in a small oncologic unit

Between 1962 and 1983 a total of 26 patients with malignant trophoblastic disease were diagnosed in northern Finland. The incidence of this disease was 1:21,000 pregnancies. Eight patients had choriocarcinoma and 18 an invasive mole. Clinically, 15 patients belonged to the nonmetastatic and 11 to the metastatic group. Of the latter, 4 patients belonged to the low-and 7 to the high-risk categories. During the first years of the study period, cytotoxic chemotherapy, mostly single-drug therapy, was often complemented with adjunctive surgery and/or irradiation. During recent years, single- or multidrug chemotherapy was supplemented with surgery in only one case with chemotherapy-resistant pulmonary metastases. All 26 patients are alive and disease-free, and after therapy 6 of them have given birth to 1-3 children. Our results suggest that malignant trophoblastic diseases can be successfully treated also in small centers of gynecologic oncology with up-to-date knowledge of the principles of modern cytotoxic chemotherapy.     

转化生长因子-β1与胎盘生长因子在葡萄胎预后中的意义

目的 探讨转化生长因子-β1(TGF-β1)与胎盘生长因子(PLGF)在葡萄胎预后中的意义.方法 收集180例葡萄胎患者,至少随访1年,其中30例发展为侵蚀性葡萄胎,1例发展为绒癌.采用免疫组化SV0002两步法检测33例正常早期妊娠(对照组)、33例未恶变葡萄胎(良性组)、31例恶变为妊娠滋养细胞肿瘤的葡萄胎(恶变组)的TGF-β1与PLGF的表达.结果 恶变组TGF-β1阳性表达率(58.1%)低于对照组(97.0%)和良性组(87.9%),差异有统计学意义(P<0.05),对照组和良性组间差异无统计学意义(P>0.05);恶变组PLGF阳性表达率(90.3%)高于对照组(36.4%)和良性组(63.6%),差异有统计学意义(P<0.05),对照组和良性组间差异无统计学意义(P>0.05).良性组和恶变组患者中年龄>40岁、人绒毛膜促性腺激素(hCG)>105 U/L、子宫体积>孕周大小者TGF-β1阳性表达率均低于无上述高危因素者(P<0.05);卵巢黄素化囊肿直径>6 cm、重复性葡萄胎患者TGF-β1阳性表达率与无上述高危因素者比较,差异均无统计学意义(P>0.05).良性组和恶变组患者中年龄>40岁、hCG>105 U/L、子宫体积>孕周大小、卵巢黄素化囊肿直径>6 cm者的PLGF阳性表达率均高于无上述高危因素者(P<0.05);有无重复性葡萄胎者PLGF阳性表达率比较,差异无统计学意义(P>0.05).良性组和恶变组中TGF-β1与PLGF表达均呈负相关(P<0.05).结论 PLGF和TGF-β1可作为预测葡萄胎恶变的参考指标,联合葡萄胎恶变的高危因素,有助于葡萄胎恶变的预测.     

Maladies trophoblastiques gestationnelles persistantes: une étude de 26 cas

Objective

This retrospective study aimed at discussing epidemioclinical criteria and therapeutic results of persistent gestational trophoblastic disease (PGTD) and choriocarcinoma throughout a series of 26 patients treated between 1990 and 2002.

Patients and methods

We reviewed the epidemioclinical records of all the patients. After aspiration, pretherapeutic work-up, and hebdomadary dosage of plasmatic HCG, patients were divided into three prognostic groups according to the Gustave-Roussy Institute (IGR) classification (hydatidiform mole, low-risk tumors, and high-risk tumors). They were treated with different chemotherapy regimens: monodrug methotrexate therapy, AE protocol (actinomycin and etoposid), and APE protocol (actinomycin, etoposid, and cisplatinum) adapted to each group.

Results

The mean age was 32 years (extremes: 20 and 49). Metrorragia and pelvic pain were themost frequent symptoms. There were 20 cases of PGTD (mole retention: three cases, invasive moles: 16 cases, and choriocarcinoma: one case) and six primary choriocarcinomas. All the evaluable patients were cured with the first-line chemotherapy or after salvage chemotherapy in patients with considerable risk for the disease who showed a resistance to monodrug methotrexate therapy. We recorded two toxic deaths with APE protocol.

Conclusions

The epidemioclinical criteria did not have any particularity. We confirmed the effectiveness of chemotherapy in PTGD. However, if we consider efficacy/toxicity ratio and the recent data of the WHO classification modified by FIGO, therapeutic deescalate may be justified at least in patients with good observance.     

Diagnostic and prognostic significance of circulating tumor suppressor gene p53 autoantibodies in patients with gestational trophoblastic tumors

Seventy-two patients with gestational trophoblastic tumors (GTTs) and 20 first-trimester healthy pregnant women (controls) participated in this study. According to the WHO scoring system, GTTs were subgrouped into 24 hydatiform mole spontaneous regression (HMSR), 18 postmolar high-risk (PMHR) and 16 low- and 14 high-risk cases of choriocarcinoma. Patients with choriocarcinoma were treated with hysterectomy and methotrexate chemotherapy, whereas molar pregnancy was managed by either oxytocin infusion followed by suction evacuation or by hysterectomy. Serum p53 autoantibodies were determined by enzyme-linked immunosorbant assay and serum hCGβ was determined by radioimmunoassay before and throughout the12 months after treatment. p53 autoantibodies were not detected in normal pregnancy and cases of HMSR but were detected in all cases of PMHR and choriocarcinoma. Concentrations of p53 autoantibodies were higher in choriocarcinoma than in PMHR cases. Serial measurements of p53 autoantibodies dropped to an undetectable level within 1 and 6 months after treatment in cases of PMHR and low-risk choriocarcinoma, respectively. Decreasing values of p53 autoantibodies in high-risk choriocarcinoma remained higher than the cut-off level of controls. There was a significant positive correlation between p53 autoantibodies and serum hCGβ concentration in GTTs. In conclusion, detection of p53 autoantibodies has a high potential for the differential diagnosis of GTTs and their serial measurements are clinically useful to monitor disease progression and to assess response to therapy in GTTs.     

13例恶性滋养细胞肿瘤膀胱转移临床分析

本文报道７７６例恶性滋养细胞肿瘤发生膀胱转移１３例，占１．７％。其中绒癌与侵蚀性葡萄贻膀胱转移分别为５．２％和０．９％。在１３例中膀胱单一转移５例，合并其它脏器转移８例，以血尿为主要症状，在全身三联序贯化疗基础上辅以膀胱灌注化疗和手术，近期完全缓解率为１００％，远期随访存活１０例，２例死于多脏器转移。提示恶性滋养细胞肿瘤膀胱转移如诊断及时，处理得当，其预后良好。