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浆液性卵巢交界性肿瘤和Ⅰ型卵巢癌中所选上皮-间质转化转录因子的表达

Expression of selected epithelial-mesenchymal transition transcription factors in serous borderline ovarian tumors and type I ovarian cancers.

作者信息

Sadlecki Pawel, Jóźwicki Jakub, Antosik Paulina, Grabiec Marek

机构信息

1 Department of Obstetrics and Gynecology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.

2 Department of Clinical Pathomorphology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.

出版信息

Tumour Biol. 2018 Jun;40(6):1010428318784807. doi: 10.1177/1010428318784807.

Abstract

Epithelial ovarian neoplasms are a heterogeneous group including tumor subsets with distinct clinicopathologic and molecular features. Recent evidence from molecular and genomic studies suggests that whereas low-grade serous carcinomas and high-grade serous carcinomas likely develop on two separate pathways, the low-grade serous carcinomas and serous borderline ovarian tumors may represent various stages of the same developmental continuum. The transformation of borderline ovarian tumors into an invasive neoplasm is associated with an array of molecular changes, inter alia controlled by p53 and PI3K/Akt pathway, as well as with a decrease in E-cadherin expression. The latter implies that epithelial-mesenchymal transition is a critical determinant of borderline ovarian tumor invasiveness. The aim of this study was to analyze the expression of transcription factors involved in epithelial-mesenchymal transition: SNAIL, SLUG, TWIST 1, TWIST 2, ZEB 1, and ZEB 2 in borderline tumors and type I ovarian cancers. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses. The expressions for SLUG, TWIST 1, ZEB1, and ZEB 2 were scored based on the nuclear staining, and the expressions of SNAIL and TWIST 2 based on the cytoplasmic and/or nuclear staining. The proportions of ovarian tumors with the immunoexpression of the epithelial-mesenchymal transition transcription factors were 85.7% for SNAIL, 100% for SLUG, 9.5% for TWIST 1, 95.2% for TWIST 2, 23.8% for ZEB 1, and 0% for ZEB 2. The expression patterns of SNAIL, SLUG, TWIST, and ZEB identified in this study suggest that both serous borderline ovarian tumors and type I ovarian cancers undergo dynamic epithelial-mesenchymal interconversions. Our findings obtained in the two groups of tumors which shared some etiopathogenic pathways imply that the expression of the epithelial-mesenchymal transition transcription factors may be activated at early stages of the epithelial-mesenchymal transition, and thus these molecules may play a pivotal role in the development of both serous borderline ovarian tumors and type I ovarian cancer.

摘要

上皮性卵巢肿瘤是一组异质性肿瘤,包括具有不同临床病理和分子特征的肿瘤亚群。分子和基因组研究的最新证据表明,低级别浆液性癌和高级别浆液性癌可能通过两条不同的途径发生发展,而低级别浆液性癌和浆液性交界性卵巢肿瘤可能代表同一发育连续体的不同阶段。交界性卵巢肿瘤向浸润性肿瘤的转变与一系列分子变化有关,尤其是受p53和PI3K/Akt通路调控,同时伴有E-钙黏蛋白表达降低。后者意味着上皮-间质转化是交界性卵巢肿瘤侵袭性的关键决定因素。本研究的目的是分析参与上皮-间质转化的转录因子:SNAIL、SLUG、TWIST 1、TWIST 2、ZEB 1和ZEB 2在交界性肿瘤和I型卵巢癌中的表达情况。该研究纳入了42例经组织病理学证实的卵巢肿物患者的组织标本。基于细胞核染色对SLUG、TWIST 1、ZEB1和ZEB 2的表达进行评分,基于细胞质和/或细胞核染色对SNAIL和TWIST 2的表达进行评分。上皮-间质转化转录因子免疫表达的卵巢肿瘤比例分别为:SNAIL为85.7%,SLUG为100%,TWIST 1为9.5%,TWIST 2为95.2%,ZEB 1为23.8%,ZEB 2为0%。本研究中鉴定出的SNAIL、SLUG、TWIST和ZEB的表达模式表明,浆液性交界性卵巢肿瘤和I型卵巢癌均经历动态的上皮-间质相互转化。我们在两组具有某些病因学途径的肿瘤中获得的研究结果表明,上皮-间质转化转录因子的表达可能在上皮-间质转化的早期阶段被激活,因此这些分子可能在浆液性交界性卵巢肿瘤和I型卵巢癌的发生发展中起关键作用。

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