Hormone receptor expression profile of low-grade serous ovarian cancers

被引:29
作者
Buttarelli, Marianna [1 ]
Mascilini, Floriana [2 ]
Zannoni, Gian Franco [3 ]
Ciucci, Alessandra [1 ]
Martinelli, Enrica [1 ]
Filippetti, Flavia [1 ]
Scambia, Giovanni [2 ]
Ferrandina, Gabriella [2 ,4 ]
Gallo, Daniela [1 ]
机构
[1] Univ Cattolica Sacro Cuore, Unit Translat Med Women & Children Hlth, Dept Obstet & Gynecol, Largo A Gemelli 8, I-00168 Rome, Italy
[2] Univ Cattolica Sacro Cuore, Dept Obstet & Gynecol, Rome, Italy
[3] Univ Cattolica Sacro Cuore, Dept Pathol, Rome, Italy
[4] Univ Molise, Dept Hlth Sci & Med, Campobasso, Italy
关键词
ER alpha; ER beta; Estradiol; Hormonal therapy; Ovary; Borderline ovarian tumor; ESTROGEN-RECEPTORS; ER-ALPHA; BETA; CARCINOMA; MICROPAPILLARY; TUMORS; CELLS; GENE; PATHWAYS; ISOFORMS;
D O I
10.1016/j.ygyno.2017.02.029
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective. Low-grade serous ovarian carcinomas (LGSOCs) are a histological subtype of epithelial ovarian tumors, accounting for fewer than 5% of all cases of ovarian carcinoma. Due to the chemoresistant nature of this subtype a search for more effective systemic therapies is actively ongoing, hormonal therapy showing some degree of activity in this clinical setting. The present study ought to investigate the hormone receptor status of LGSOCs, as a strategy to provide molecular support for patient-tailored hormonal treatments. Methods. Estrogen receptor a. (ER alpha), ER beta isoforms (i.e. ER beta 1, ER beta 2 and ER beta 5), progesterone and androgen receptor (PR, AR) expression was evaluated by immunohistochemistry in 25 untreated LGSOC primary tumors, 6 matched metastases and 6 micropapillary variant of serous borderline tumors (micropapillary SBOTs). In vitro cellular models were used to provide insights into clinical observations. Results. Our results showed prominent expression of nuclear ER alpha, ER beta 2, ER beta 5 and PR in LGSOC primarY tissues, while metastatic lesions also exhibit considerable cytoplasmic ER beta 2 levels. Notably, a higher expression of ERS1 protein was determined in micropapillary SBOTs compared to LGSOCs. In vitro experiments on LGSOC cell lines (i.e. HOC-7 and VOA-1056) revealed low/absent ER alpha, PR and AR protein expression, whereas the three ER beta isoforms were all present. Proliferation of HOC-7 and VOA-1056 was not modulated by either the endogenous or the selective synthetic ligands. Conclusions. These novel findings highlight the need of assessing relative levels of ER alpha and ER beta isoforms in the total receptor pool in future clinical studies investigating molecular predictors of response to hormonal therapy in LGSOC. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:352 / 360
页数:9
相关论文
共 40 条
[1]  
[Anonymous], EXPERT REV ANTICANCE
[2]   Nuclear hormone receptors and gene expression [J].
Aranda, A ;
Pascual, A .
PHYSIOLOGICAL REVIEWS, 2001, 81 (03) :1269-1304
[3]   Ubiquitin-proteasome system stress sensitizes ovarian cancer to proteasome inhibitor-induced apoptosis [J].
Bazzaro, M ;
Lee, MK ;
Zoso, A ;
Stirling, WLH ;
Santillan, A ;
Shih, IE ;
Roden, RBS .
CANCER RESEARCH, 2006, 66 (07) :3754-3763
[4]   Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor [J].
Bazzaro, Martina ;
Lin, Zhenhua ;
Santillan, Antonio ;
Lee, Michael K. ;
Wang, Mei-Cheng ;
Chan, Kwun C. ;
Bristow, Robert E. ;
Mazitschek, Ralph ;
Bradner, James ;
Roden, Richard B. S. .
CLINICAL CANCER RESEARCH, 2008, 14 (22) :7340-7347
[5]   Micropapillary serous carcinoma of the ovary - A distinctive low-grade carcinoma related to serous borderline tumors [J].
Burks, RT ;
Sherman, ME ;
Kurman, RJ .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1996, 20 (11) :1319-1330
[6]  
Carcangiu ML., 2014, WHO Classification of Tumours of Female Reproductive Organs
[7]   Breast tumor aromatase: functional role and transcriptional regulation [J].
Chen, S ;
Zhou, D ;
Okubo, T ;
Kao, YC ;
Yang, C .
ENDOCRINE-RELATED CANCER, 1999, 6 (02) :149-156
[8]   Multiple direct and indirect mechanisms drive estrogen-induced tumor growth in high grade serous ovarian cancers [J].
Ciucci, Alessandra ;
Zannoni, Gian Franco ;
Buttarelli, Marianna ;
Lisi, Lucia ;
Travaglia, Daniele ;
Martinelli, Enrica ;
Scambia, Giovanni ;
Gallo, Daniela .
ONCOTARGET, 2016, 7 (07) :8155-8171
[9]   Mitochondrial estrogen receptor β2 drives antiapoptotic pathways in advanced serous ovarian cancer [J].
Ciucci, Alessandra ;
Zannoni, Gian Franco ;
Travaglia, Daniele ;
Scambia, Giovanni ;
Gallo, Daniela .
HUMAN PATHOLOGY, 2015, 46 (08) :1138-1146
[10]   Prognostic significance of the estrogen receptor beta (ERβ) isoforms ERβ1, ERβ2, and ERβ5 in advanced serous ovarian cancer [J].
Ciucci, Alessandra ;
Zannoni, Gian Franco ;
Travaglia, Daniele ;
Petrillo, Marco ;
Scambia, Giovanni ;
Gallo, Daniela .
GYNECOLOGIC ONCOLOGY, 2014, 132 (02) :351-359