Expression of maspin in gestational trophoblastic disease

Expression of maspin in gestational trophoblastic disease
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DOI:
10.1016/j.ygyno.2005.09.037
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发表时间:
2006-04-01
影响因子:
4.7
通讯作者:
Wong, YF
Wong, YF
中科院分区:
医学2区
文献类型:
--
作者:
Li, HWR;Leung, SW;Wong, YF

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背景Maspin是一种肿瘤抑制基因,其表达在许多组织的瘤形成和恶性肿瘤中改变。在人胎盘中,maspin基因在滋养层细胞中表达,可能作为滋养层细胞侵袭的抑制性调节剂。因此,在妊娠滋养细胞疾病(GTD)中,滋养细胞组织的侵袭倾向增加,我们假设maspin表达会降低。本研究旨在探讨maspin在GTD中的表达及其与预后的关系。采用免疫组织化学方法,首先研究maspin在葡萄胎中的表达,并以孕龄匹配的正常早孕胎盘作为对照。共研究了38例葡萄胎病例,包括20例完全葡萄胎(CM)和18例部分葡萄胎(PM)。其中,CM组10例和PM组8例随后发生妊娠滋养细胞肿瘤(GTN)。对4例绒毛膜癌和5例胎盘部位滋养细胞肿瘤的组织也进行了免疫组化染色。应用逆转录-聚合酶链反应(RT-PCR)技术对10例葡萄胎(5例合并GTN,5例未合并GTN)和6例正常早孕胎盘组织中的RNA进行检测。在所有组织切片中,证实了免疫染色信号的核表达,主要在细胞滋养层中。完全性和部分性葡萄胎滋养细胞核染色百分率均明显低于正常早孕胎盘(P < 0.001)。而完全性和部分性葡萄胎的免疫组化染色差异无统计学意义(P > 0.05)。随后发生GTN的病例中maspin的表达也显著低于未发生GTN的病例(P = 0.01)。绒毛膜癌和胎盘部位滋养细胞肿瘤的免疫组化染色显示,所有肿瘤细胞中maspin的表达均降低。逆转录-聚合酶链反应显示,在所有的葡萄胎标本中,maspin的表达均持续下调。我们的研究结果表明,maspin在妊娠滋养细胞疾病中表达下调,并且在妊娠滋养细胞肿瘤中表达下调更为明显。这可能在葡萄胎的发病机制和恶变中发挥具有预后意义的作用。(C)2005年爱思唯尔公司All rights reserved.
Background. Maspin is a tumor suppressor gene whose expression is altered in neoplasia and malignancies of many tissues. In the human placenta, the maspin gene is expressed in trophoblastic cells and might act as an inhibitory regulator of trophoblastic invasion. Hence, in gestational trophoblastic disease (GTD), where there is increased propensity for invasion in the trophoblastic tissue, we hypothesized that maspin expression would be decreased. The present study aimed at investigating the expression of maspin in GTD and its prognostic significance.Methods. Using immunohistochemical staining, we firstly studied the expression of maspin in hydatidiform moles, with gestational age-matched normal first trimester placenta used as control. A total of 38 cases of hydatidiform moles were studied, including 20 complete moles (CM) and 18 partial moles (PM). Among them, 10 cases of the CM group and 8 cases of the PM group subsequently developed gestational trophoblastic neoplasia (GTN). Immunostaining was also performed on tissue from 4 cases of choriocarcinoma and 5 cases of placental site trophoblastic tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was further performed on RNA extracted from 10 hydatidiform moles (5 with GTN and 5 without) and 6 normal first-trimester placentae.Results. In all tissue sections, nuclear expression of immunostaining signal was demonstrated, mainly in the cytotrophoblasts. The percentage of trophoblastic nuclei stained in both complete and partial moles was significantly lower than that in normal first-trimester placenta ( P < 0.001). However, there was no significant difference in immunostaining between complete and partial moles (P > 0.05). There was also significantly lower expression of maspin in those cases subsequently developing GTN than those which did not (P = 0.01). Immunostaining on choriocarcinoma and placental site trophoblastic tumor showed reduced expression of maspin in all the tumor cells. Reverse transcriptase-polymerase chain reaction revealed that the expression of maspin was consistently down-regulated in all the hydatidiform mole samples.Conclusions. Our results suggest that there is down-regulated expression of maspin in gestational trophoblastic diseases, and the downregulation is more prominent in cases developing gestational trophoblastic neoplasia. This may play a role with prognostic significance in the pathogenesis and malignant transformation of hydatidiform moles. (C) 2005 Elsevier Inc. All rights reserved.