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乳腺丝抑蛋白在妊娠滋养细胞疾病中的表达

Expression of maspin in gestational trophoblastic disease.

作者信息

Li H W Raymond, Leung See Wai, Cheung Annie N Y, Yu May M Y, Chan Loucia K Y, Wong Yick Fu

机构信息

Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

出版信息

Gynecol Oncol. 2006 Apr;101(1):76-81. doi: 10.1016/j.ygyno.2005.09.037. Epub 2005 Nov 4.

Abstract

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 down-regulation 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.

摘要

背景

Maspin是一种肿瘤抑制基因,其表达在许多组织的肿瘤形成和恶性肿瘤中发生改变。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因子。因此,在滋养层组织侵袭倾向增加的妊娠滋养细胞疾病(GTD)中,我们推测maspin表达会降低。本研究旨在调查maspin在GTD中的表达及其预后意义。

方法

我们首先使用免疫组织化学染色研究maspin在葡萄胎中的表达,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,包括20例完全性葡萄胎(CM)和18例部分性葡萄胎(PM)。其中,CM组10例和PM组8例随后发生了妊娠滋养细胞肿瘤(GTN)。还对4例绒毛膜癌和5例胎盘部位滋养细胞肿瘤的组织进行了免疫染色。对从10例葡萄胎(5例发生GTN,5例未发生)和6例正常早孕胎盘提取的RNA进一步进行逆转录聚合酶链反应(RT-PCR)。

结果

在所有组织切片中,均显示免疫染色信号的核表达,主要在细胞滋养层细胞中。完全性和部分性葡萄胎中染色的滋养层细胞核百分比均显著低于正常早孕胎盘(P < 0.001)。然而,完全性和部分性葡萄胎之间的免疫染色无显著差异(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染色显示所有肿瘤细胞中maspin表达降低。逆转录聚合酶链反应显示,所有葡萄胎样本中maspin的表达均持续下调。

结论

我们的结果表明,妊娠滋养细胞疾病中maspin表达下调,在发生妊娠滋养细胞肿瘤的病例中下调更为明显。这可能在葡萄胎的发病机制和恶性转化中具有预后意义。

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