滋养叶细胞增殖基因及间质细胞凋亡检测在水泡状胎块诊断中的价值

目的探讨滋养叶细胞增殖相关基因及间质细胞凋亡检测在水泡状胎块（HM）病理诊断中的价值。方法应用免疫组织化学标记技术,检测100 例HM（其中完全性HM 61 例,部分性HM 39 例）及40 例绒毛水肿的病理组织标本滋养叶细胞的Ki67、Livin与Bcl-2 的表达,并应用TUNEL法对绒毛间质凋亡细胞进行原位观察。结果Ki67 阳性表达在绒毛水肿组、部分性HM 组、完全性HM 组趋势呈逐渐增强,各组间比较均差异有统计学意义（P <0.05）;绒毛水肿组及HM 组绒毛间质内AI指数比较,差异有统计学意义（P <0.05）;Livin 及Bcl-2 表达差异无统计学意义（P >0.05）;Ki67 表达与AI 指数呈正相关（P <0.05）。结论间质细胞凋亡联合滋养叶细胞中Ki67 表达检测可用于HM的诊断与分型,也可用于鉴别HM 与绒毛水肿。     

The value of PAPP-A in the diagnosis and prognosis of GTD

Objective: To investigate the value of PAPP-A (pregnancy assouated plasma protein-A) in the diagnosis and prognosis of gestational trophoblastic disease (GTD). Methods: The serum β-HCG (β-human chorionic gonadotropin) and PAPP-A levels of 25 normal pregnant women, 28 patients with complete hydatidiform mole and 38 patients with invasive mole were measured by enzyme linked immunosorbent assay (ELISA) during the periods of diagnosis, treatment and follow-up. Results: Compared with control group, patients with complete mole and invasive mole had higher levels of β-HCG (P ＜ 0.01 ). But there was no significant difference between the complete and invasive mole group (P ＞ 0.05). The PAPP-A level of complete mole group was significantly higher than that of control group (P ＜ 0.01). The PAPP-A level of invasive mole group was significantly higher than that of complete mole group and control group(P ＜ 0.05). In complete mole group, serum β-HCG and PAPP-A levels of the patients with malignant sequelae were significantly higher than those with benign sequelae (P ＜ 0.05). The β-HCG level had no relationship with the clinical stage of invasive mole. However, the PAPP-A level increased with clinical advancement of invasive mole. The levels of β-HCG and PAPP-A gradually decreased after evacuation in patients with complete moles, but maintained positive or even increased in patients with subsequent malignancy. Conclusion: The PAPP-A level can give us some help not only in early diagnosis of hydatidiform mole and invasive mole, but also in the prognosis of malignant sequelae.     

Trichosanthin in the treatment of hydatidiform mole. Clinical analysis of 52 cases.

During 1972-1986, 44 of 52 patients (84.6%) with hydatidiform mole were treated successfully with trichosanthin. Of these, 38 (73.1%) had complete spontaneous evacuation and 6 (11.5%) incomplete evacuation. The average time for evacuation of hydatidiform mole was 4.5 +/- 1.64 days. The amount of bleeding was less than 100 ml in 33 patients (75%), while that in 2 of the patients with incomplete evacuation was more than 300 ml. Malignant changes occurred in two of the 44 patients (4.5%). The malignant rate was similar to that (4-12.5, P greater than 0.05) of prophylactic chemotherapy. We consider that thrichosanthin is a better approach to the treatment of hydatidiform mole.

     

滋养细胞疾病患者血浆纤维结合蛋白的检测意义

目的 探讨血浆纤维结合蛋白(PFn)与良恶性滋养细胞疾病的相关性.方法 62例恶性滋养细胞疾病患者(绒癌35例,侵蚀性葡萄胎27例),54例良性葡萄胎患者及同年龄组健康献血员100例,进行PFn及人绒毛膜促性腺激素(β-HCG)测定.结果 发现恶性滋养细胞疾病组PFn浓度较良性葡萄胎组及健康对照组极明显降低(P＜0.01);而良性葡萄胎组与健康对照组间无显著性差异.结论 PFn可协助诊断恶性滋养细胞疾病,特别在鉴别诊断良、恶性滋养细胞疾病时有一定意义.PFn尚不能作为判断化疗效果的敏感指标.     

E—cad和VEGF在妊娠滋养细胞疾病中的表达及意义

目的观察E—cad和VEGF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,所有病例均经病理确诊。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E-cad和VEGF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E—cad在正常早孕绒毛、葡萄胎、侵蚀性葡萄胎和绒癌中的表达逐渐降低,分别为3．521,3．1045,0．9655,0．7682,各组差异有统计学意义（P〈0．05）;VEGF在正常早孕绒毛、葡萄胎、侵蚀性葡萄胎和绒癌中的表达逐渐升高,分别为0．4219,0．7521,0．9611,1.1420,各组差异有统计学意义（P〈0.05）。结论①E-cad在滋养细胞肿瘤和葡萄胎中的表达均低于正常绒毛组织,E-cad表达减弱与GTT恶性进展有关,对于良、恶性葡萄胎鉴别有重要意义。②E—cad和VEGF的表达变化,使滋养细胞粘附异常,侵蚀性增强,是滋养细胞疾病发生的重要途径之一。     

葡萄胎发病新基因F10与滋养细胞肿瘤侵袭相关性研究

OBJECTIVE: To study the expressions of the novel gene F10 associated with hydatidiform mole in different trophoblastic tumors and explore the relation of F10 expression with the invasiveness of malignant trophoblastic tumor. METHODS: In situ hybridization was used to study the expression of F10 in 12 cases of hydatidiform mole, 6 cases of invasive mole, and 8 cases of choriocarcinoma. RESULTS: F10 mRNA was positive in all cases of hydatidiform mole, invasive mole, and choriocarcinoma, and the expression intensity significantly increased in the order of hydatidiform mole, invasive mole and choriocarcinoma (P<0.001). CONCLUSION: The expression of F10 gene may relate to the occurrence and invasiveness of trophoblastic tumor, with possible involvement in the invasion or malignant changes of trophoblastic cells.     

葡萄胎发病新基因F10与滋养细胞肿瘤侵袭相关性研究

目的 探讨葡萄胎差异表达新基因F10在不同类型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 采用原位杂交方法检测12例葡萄胎、6例侵袭性葡萄胎、8例绒癌中F10表达情况。结果 F10在全部葡萄胎、侵袭性葡萄胎、绒癌中均呈阳性表达,其在葡萄胎、侵袭性葡萄胎、绒癌中的表达强度递增,有显著性差异(P<0.001)。结论 F10可能与滋养细胞肿瘤的发生及其侵袭行为相关,在侵袭或滋养细胞恶变中起一定作用。     

Genetically identified complete hydatidiform mole coexisting with a normal fetus following IVF-ET

A complete hydatidiform mole coexisting with a fetus following in vitro fertilization and embryo transfer （IVF-ET） is a rare event. The diagnosis is often not easy because of the morphological similarity to a partial mole, but important to the treatment. We present a recent case in which STR polymorphism analysis clearly revealed a different genetic origin for the fetal and molar parts. STR polymorphisms on 15 variable number tandem repeat loci and a gender-determination locus, which were detected by polymerase chain reaction, indicating that the cord/placenta and molar tissue were parental and androgenous, respectively. During follow-up, the patient developed persistent gestational trophoblastic tumor （GTT） which was successfully treated with chemotherapy. In this case, STR polymorphism analysis exactly diagnosed a twin pregnancy consisting of a complete hydatidiform mole and a fetus.     

A perplexing case of gastrointestinal haemorrhage

Choriocarcinoma is a gestational trophoblastic tumour with a high metastatic potential but presentation with gastrointestinal haemorrhage due to jejunal mucosal metastasis is very rare. A 25-year-old Nepali woman presented with severe anaemia and massive gastrointestinal haemorrhage after normal pregnancy following evacuation of a hydatiform mole. During laparotomy, the patient was found to have extensive jejunal mucosal metastases.     

妊娠滋养细胞肿瘤阴道转移13例临床分析

目的评估妊娠滋养细胞肿瘤阴道转移患者的临床表现、治疗方法及疗效。方法选择1991年8月~2015年8月我院妇科收治的13例妊娠滋养细胞肿瘤阴道转移患者临床资料进行研究。结果侵蚀性葡萄胎和绒毛膜癌阴道转移的发生率分别为8.9%和8.2%,其中7例发生破溃大出血。治疗方法采用以5-FU为主的联合化疗或EMA-CO方案化疗,7例大出血患者进行阴道填塞,另3例大出血患者因填塞效果差行选择性动脉栓塞术。13例中12例经1~8个疗程的化疗后,获得完全缓解,经定期随访,无复发迹象,1例合并脑转移化疗期间因耐药病情恶化死亡。结论以5-FU为主的联合化疗、局部注射5-FU是治疗妊娠滋养细胞肿瘤阴道转移的有效方法。选择性盆腔动脉栓塞术对于难以控制的转移结节大出血具有重要的临床治疗价值。     

错配修复基因启动子甲基化和蛋白表达在葡萄胎的发生及恶变中的作用

目的探讨错配修复基因hMLH1和hMSH2启动子甲基化和蛋白表达在葡萄胎的发生及恶变中的作用.方法用甲基化敏感性核酸内切酶HpaⅡ酶切-PCR法,分析正常早孕人流绒毛、部分性葡萄胎(PM)、完全性葡萄胎(CM)和侵蚀性葡萄胎(IM)hMLH1和hMSH2启动子甲基化情况;免疫组化检测hMLH1和hMSH2原位蛋白表达.结果在正常早孕绒毛、PM、CM和IM组织中,hMLH1和hMSH2均表达于细胞滋养细胞,合体滋养细胞大多表达阴性,极少数为弱阳性.正常早孕绒毛组织均未发现hMLH1和hMSH2启动子甲基化,而hMLH1和hMSH2表达全部阳性,阳性率为100%,与PM、CM组织相比,启动子甲基化和蛋白表达均存在显著性差异(P＜0.05).IM中hMLH1和hMSH2启动子甲基化发生率分别为80.0%(12/15)和73.3%(11/15),与PM、CM相比无显著性差异(P＞0.05);IM hMLH1蛋白表达阳性率为54.5%(6/11),与PM、CM相比无显著性差异(P＞0.05);而hMSH2蛋白表达阳性率为36.4%(4/11),明显弱于CM,两者比较有显著性差异(P=0.044).CM和IM组织中hMSH2启动子甲基化与其蛋白表达间存在相关性(P值分别=0.001和0.039).结论hMLH1和hMSH2的高表达对正常细胞滋养细胞基因组的稳定性起着重要的作用;hMLH1和hMSH2启动子甲基化的发生和蛋白表达的缺失参与了葡萄胎的发生.     

Fas及FasL在葡萄胎、侵蚀性葡萄胎中的表达及意义

目的 探讨Fas及FasL蛋白在妊娠滋养细胞疾病中的表达及意义. 方法 应用免疫组化方法分别检测Fas及FasL蛋白在40例正常滋养细胞、36例完全性葡萄胎和15例侵蚀性葡萄胎中的表达. 结果 Fas在侵蚀性葡萄胎组、完全性葡萄胎组和正常滋养细胞组的阳性表达率分别为46.7%,88.9%和95.0%.在侵蚀性葡萄胎组的Fas阳性表达率与完全性葡萄胎组、正常滋养细胞组差异有统计学意义(P<0.05),FasL在侵蚀性葡萄胎组、完全性葡萄胎组和正常滋养细胞组的阳性表达率分别为53.3%,44.4%和17.5%.在完全性葡萄胎组、侵蚀性葡萄胎组的FasL阳性表达率与正常滋养细胞组差异有统计学意义(P<0.05).Fas与FasL表达在各组之间均呈负相关. 结论 Fas蛋白的低表达及FasL的高表达降低了妊娠滋养细胞疾病的凋亡,可能是妊娠滋养细胞疾病的发病机制之一.两者在妊娠滋养细胞疾病进展中可能相互影响,起协同作用.     

NDPK/nm23基因在滋养细胞肿瘤中的表达及其意义

目的：探讨ｎｍ２３基因表达产物（ＮＤＰＫ）在滋养细胞中的表达及其意义。方法：采用免疫组织化学方法,检测经病理证实的正常绒毛（２５例）、葡萄胎（３０例）、侵蚀性葡萄胎（２５例）、绒毛膜癌（２６例）组织中ＮＤＰＫ／ｎｍ２３的表达状况。结果：①５１例滋养细胞肿瘤中ＮＤＰＫ／ｎｍ２３的阳性表达率为１５．７％（８／１５）,远低于正常绒毛组织７６．０％（１９／２５）,差异有高度显著性（Ｐ＜０．０１）。②葡萄胎、侵蚀性葡萄胎和绒毛膜癌中ＮＤＰＫ／ｎｍ２３的阳性表达率分别为６６．７％、２８．０％、３．９％,差异有显著性（Ｐ＜００５）。③伴有转移的１４例滋养细胞肿瘤中,无１例ＮＤＰＫ／ｎｍ２３阳性表达。④ＮＤＰＫ／ｎｍ２３在葡萄胎中阳性表达率稍低于正常绒毛对照组,差异无显著性（Ｐ＞００５）。结论：ＮＤＰＫ／ｎｍ２３的低表达或不表达与滋养细胞肿瘤的发生、转移、恶性程度及预后密切相关。     

妊娠滋养细胞肿瘤中PCNA表达的研究

目的：研究妊娠滋养细胞肿瘤(GTT)中PCNA的表达意义。方法：采用免疫组化S—P法检测了10例正常早期绒毛(NP)、10例完全性葡萄胎(CM)、20例侵袭性葡萄胎(IM)、19例绒癌(CCA)中PC—NA的表达。结果：PCNA在NP、CM、IM和CCA中表达率分别为10．40％、20．76％、53．60％、51．95％，各组间差异有统计学意义。结论：恶性GTT、中细胞增殖活性增高，PCNA的检测有助于良恶性GTT的鉴别。     

155例妊娠滋养细胞疾病临床资料分析

目的 探讨妊娠滋养细胞疾病的临床特征、治疗、预后及随访情况。 方法 收集2008年1月-2013年10月因妊娠滋养细胞疾病入住安徽医科大学第一附属医院155例患者的临床资料,其中葡萄胎99例,滋养细胞肿瘤56例。按年龄分组:<25岁35人,25~35岁49人,>35岁71人。妊娠次数为1次、2次、3次、≥ 4次分别有20、48、55、32人。 结果 患者年龄17~52岁,平均31.7岁;其中年龄>35岁占45.8%,明显高于年龄<25岁组及25~35岁组。。155例患者中妊娠次数为2,3, ≥ 4次分别占31.0%,35.5%,20.6%,与初次妊娠即发病者所占12.9%相比明显增高(P<0.05)。99例葡萄胎患者中行清宫术51例,二次清宫术32例,预防性化疗+清宫术8例,预防性化疗+子宫切除术8例。56例滋养细胞肿瘤患者行MTX单药化疗9例,5-FU单药化疗12例,EMA-Co方案9例,BEP方案8例,VP+DDP方案2例,5-FU+KSM方案16例。化疗疗程3~11个,平均5.47个。葡萄胎的恶变率达12.1%。妊娠滋养细胞肿瘤的治愈率达85.7%。 结论 年龄及既往孕次和妊娠滋养细胞疾病的发生有关:年龄>35岁,妊娠滋养细胞疾病的风险增高;既往有妊娠史者较初孕者发生妊娠滋养细胞疾病的风险高。葡萄胎有恶变倾向,因此,早期诊断、治疗和严密随访至关重要。      

Expression of c-erbB2 in gestational trophoblastic disease and its clinical significance

Summary: In order to explore a potential indicator of predicting the occurrence and development of gestational trophoblastic tumor, the expression of c-erbB2 oncogene in human normal placenta, hyda tidiform mole and choriocarcinoma was investigated. The expression of c-erbB2 was detected im munohistochemically by monoclonal antibody against the gene on the formalin-fixed paraffin sections of 21 hydatidiform moles, 21 invasive moles, 20 choriocarcinomas and 30 normal placentas. Results showed that the expression level of c-erbB2 was significantly higher in gestational trophoblastic tumor than in hydatidiform mole and normal placenta of midterm and term pregnancy (P＜0. 05), while there was no significant difference between patients with gestational trophoblastic tumor of stage Ⅲ ,Ⅳ and those of stage Ⅰ , Ⅱ . It was demonstrated that overexpression of c-erbB2 may closely associ ated with malignant transformation of hydatidiform mole, not only providing important insight into pathogenesis of gestational trophoblastic tumor, but also having an important significance for the ear-ly diagnosis and early treatment of gestational trophoblastic tumor.     

妊娠滋养细胞肿瘤中细胞凋亡原位观察

目的:探讨妊娠滋养细胞肿瘤(GTT)中的细胞凋亡情况.方法:采用核酸原位末端标记(TUNEL)法,检测10例正常早期绒毛(NP)、10例完全性葡萄胎(CM)、20例侵袭性葡萄胎(IM)、19例绒癌(CCA)中的细胞凋亡.结果:在NP、CM、IM和CCA中,细胞凋亡指数(AI)分别为1.88%、2.59%、6.45%、1.26%,各组间差异有统计学意义,(F=7.020,P=0.000).其中,在IM与CCA之间,差异有统计学意义(P=0.009).结论:GTT的发生是由于机体监控能力减弱或消失、增殖与凋亡调节系统失调所致.     

TGF-β1和PLGF在不同类型妊娠滋养细胞疾病患者病变组织中的表达及其意义

目的：检测不同类型妊娠滋养细胞疾病患者病变组织中转化生长因子β1（TGF-β1）和胎盘生长因子（PLGF）的表达,阐明其在不同妊娠滋养细胞疾病中意义。方法：收集葡萄胎组织40例（葡萄胎组）、妊娠滋养细胞肿瘤组织26例（GTN组,包括侵蚀性葡萄胎22例和绒毛膜癌4例）和正常早孕绒毛组织40例（正常对照组）作为研究对象。采用免疫组织化学法检测不同组织中TGF-β1和PLGF的阳性表达率,分析TGF-β1和PLGF在正常对照组、葡萄胎组和GTN组患者中的表达差异以及其与患者临床高危因素（年龄>40岁、子宫体积>孕周和卵巢黄素化囊肿直径>6 cm）的关联性。结果：与正常对照组（87.5%）比较,葡萄胎组（62.5%）和GTN组（30.8%）TGF-β1阳性表达率明显降低（P<0.05）;且葡萄胎组TGF-β1阳性表达率高于GTN组（P<0.05）。与正常对照组（22.5%）比较,葡萄胎组（50.0%）和GTN组（80.8%）PLGF阳性表达率明显升高（P<0.05）,且葡萄胎组PLGF阳性表达率低于GTN组（P<0.05）。与正常对照组比较,葡萄胎组患者中年龄>40岁、子宫体积>孕周、卵巢黄素化囊肿直径>6 cm者TGF-β1阳性表达率明显降低（P<0.05）,而PLGF阳性表达率明显升高（P<0.05）。在GTN组中并发高危因素者较无高危因素者TGF-β1阳性表达率明显降低（P<0.05）,而PLGF阳性表达率明显升高（P<0.05）。葡萄胎组和GTN组患者TGF-β1与PLGF阳性表达水平均呈负相关关系（r=-0.585,P<0.05;r=-0.479,P<0.05）。结论：TGF-β1在葡萄胎和妊娠滋养细胞肿瘤组织中阳性表达逐渐降低,PLGF表达率逐渐升高,可能与妊娠滋养细胞疾病患者的不同类型及预后有关。     

妊娠滋养细胞疾病研究进展

妊娠性滋养细胞疾病是来源于胎盘滋养细胞的一组疾病,包括葡萄胎、侵蚀性葡萄胎、胎盘部位滋养细胞肿瘤和绒毛膜癌,是严重威胁女性健康的妇科疾病之一。随着化疗药物的应用,滋养细胞肿瘤治愈率达80%～90%,成为最早可经化疗治愈的恶性肿瘤之一。妊娠滋养细胞疾病的发生、发展是多因素参与、极其复杂的病理过程。现代医学研究对该疾病的发生机制有进一步的认识。     

Update on molar pregnancy and choriocarcinoma

The term gestational trophoblastic disease encompasses a wide spectrum of disorders ranging from the benign hydatidiform mole to the malignant choriocarcinoma and placental site trophoblastic tumor. Recent advances in cytogenetics and pathological criteria have brought to light the occurrence of the partial mole, which is probably more common than the complete mole. The World Health Organisation has proposed a classification to rectify the current confusion that exists with clinical and pathological terms. Evacuation of the uterus followed by meticulous followup with sensitive beta subunit Human Chorionic Gonadotropin assay remain the cornerstone of management of molar pregnancy. Prompt chemotherapy is the most important aspect in managing malignant sequelae. Newer chemotherapy regimes have helped to salvage failures from the usual drugs. Judicial use of surgery in metastatic trophoblastic disease can reduce the duration and toxicity of chemotherapy. All patients with gestational trophoblastic disease should be managed in a tertiary care centre with the expertise and facilities easily available to manage these cases.