Buttarelli Marianna, Mascilini Floriana, Zannoni Gian Franco, Ciucci Alessandra, Martinelli Enrica, Filippetti Flavia, Scambia Giovanni, Ferrandina Gabriella, Gallo Daniela
Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Gynecol Oncol. 2017 May;145(2):352-360. doi: 10.1016/j.ygyno.2017.02.029. Epub 2017 Feb 20.
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.
Estrogen receptor α (ERα), ERβ isoforms (i.e. ERβ1, ERβ2 and ERβ5), 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.
Our results showed prominent expression of nuclear ERα, ERβ2, ERβ5 and PR in LGSOC primary tissues, while metastatic lesions also exhibit considerable cytoplasmic ERβ2 levels. Notably, a higher expression of ERβ1 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 ERα, PR and AR protein expression, whereas the three ERβ isoforms were all present. Proliferation of HOC-7 and VOA-1056 was not modulated by either the endogenous or the selective synthetic ligands.
These novel findings highlight the need of assessing relative levels of ERα and ERβ isoforms in the total receptor pool in future clinical studies investigating molecular predictors of response to hormonal therapy in LGSOC.
低级别浆液性卵巢癌（LGSOCs）是上皮性卵巢肿瘤的一种组织学亚型，占所有卵巢癌病例的比例不到5%。由于该亚型具有化疗耐药性，目前正在积极寻找更有效的全身治疗方法，激素疗法在这种临床情况下显示出一定程度的活性。本研究旨在调查LGSOCs的激素受体状态，为针对患者的激素治疗提供分子支持。
通过免疫组织化学评估25例未经治疗的LGSOC原发性肿瘤、6例匹配的转移灶和6例浆液性交界性肿瘤微乳头变体（微乳头SBOTs）中雌激素受体α（ERα）、ERβ亚型（即ERβ1、ERβ2和ERβ5）、孕激素和雄激素受体（PR、AR）的表达。体外细胞模型用于深入了解临床观察结果。
我们的结果显示，LGSOC原发性组织中核ERα、ERβ2、ERβ5和PR表达显著，而转移灶的细胞质ERβ2水平也相当高。值得注意的是，与LGSOCs相比，微乳头SBOTs中ERβ1蛋白表达更高。对LGSOC细胞系（即HOC-7和VOA-1056）的体外实验显示，ERα、PR和AR蛋白表达低/无，而三种ERβ亚型均存在。HOC-7和VOA-1056的增殖不受内源性或选择性合成配体的调节。
这些新发现突出了在未来调查LGSOC激素治疗反应分子预测指标的临床研究中，评估总受体库中ERα和ERβ亚型相对水平的必要性。
