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Steroid hormone synthesis by the ovarian stroma surrounding epithelial ovarian tumors: a potential mechanism in ovarian tumorigenesis.

卵巢上皮性肿瘤周围的卵巢间质合成类固醇激素:卵巢肿瘤发生的可能机制。

Blanco LZ,Kuhn E,Morrison JC,Bahadirli-Talbott A,Smith-Sehdev A,Kurman RJ
阅读:1443 Modern PathologyApr 2017; 30 (4): 472 - 629:563-576 

Abstract

Epithelial ovarian tumors are responsive to steroid hormone stimulation and the ovarian stroma may have a direct role in this process. We evaluated immunohistochemical markers of sex-steroid differentiation and steroidogenesis (calretinin, inhibin, steroidogenic factor 1), steroid enzymes involved in hormone biosynthesis (CYP17, CYP19, HSD17β1, AKR1C3), and hormone receptors (estrogen receptor, progesterone receptor, and androgen receptor) in 101 epithelial ovarian tumors and in normal structures implicated in ovarian carcinogenesis (ovarian surface epithelium and cortical inclusion cysts) in an attempt to elucidate this process. We hypothesized that ovarian stroma immediately adjacent to tumors express markers of sex-steroid differentiation and steroidogenesis and steroid enzymes whereas the epithelium contains corresponding hormone receptors. As the findings in seromucinous, endometrioid, and clear cell neoplasms, tumors closely associated with endometriosis, were very similar, these were combined into a group designated 'endometriosis-related tumors.' Significantly increased expression of markers of sex-steroid differentiation and steroidogenesis was found in stroma immediately adjacent to endometriosis-related tumors (P=0.003) and mucinous tumors (primary and metastatic mucinous tumors were combined because of similar findings) (P<0.0001) compared with more remote ovarian stroma. In addition, sex-steroid enzymes were increased in stroma adjacent to endometriosis-related tumors (P=0.02) and mucinous tumors (P=0.02) compared with more distant stroma. Steroid hormone receptors showed greater expression in epithelium compared with stroma in the endometriosis-related tumors (P=0.0009), low-grade serous tumors (P<0.0001), and high-grade serous carcinoma (P=0.0036). In contrast, there was greater expression in stroma compared with epithelium (P<0.0001) in mucinous tumors, which may be due to the fact that they are not derived from müllerian epithelium. In conclusion, our findings strongly support the view that the stroma surrounding epithelial tumors in the ovary is activated to elaborate steroid hormones which may stimulate further neoplastic growth. The precise mechanisms by which this process might occur are complex and require further investigation.

摘要

卵巢上皮性肿瘤对类固醇激素刺激有反应,卵巢间质可能在这一过程中起直接作用。我们评估了101例卵巢上皮性肿瘤及与卵巢癌发生密切相关的正常卵巢结构(卵巢表面上皮细胞和皮质包含囊肿)中性激素分化和类固醇激素生成(钙结合蛋白、抑制素、类固醇生成因子1)、类固醇激素生物合成相关酶(CYP17、CYP19,HSD17β1、AKR1C3)及激素受体(雌激素受体、孕激素受体和雄激素受体)的免疫组化标记,试图阐明这一过程。我们假设紧邻肿瘤的卵巢间质表达性激素分化的类固醇标记物,而上皮细胞包含相应的激素受体。由于浆粘液性、子宫内膜样与透明细胞肿瘤(与子宫内膜异位症密切相关的肿瘤)结果非常相似,因此这些肿瘤组成一组,命名为“子宫内膜异位症相关的肿瘤”。与较远的卵巢间质相比,性激素分化和类固醇激素生成标志物在子宫内膜异位症相关肿瘤(P=0.003)和黏液性肿瘤(原发性和转移性黏液性肿瘤因为类似的结果被组合到一起)(P<0.0001)的临近卵巢间质中表达显著增加。此外,与较远的卵巢间质相比,临近子宫内膜异位症相关的肿瘤(P = 0.02)和粘液性肿瘤(P = 0.02)的卵巢间质中性类固醇激素相关酶表达增加。在子宫内膜异位症相关肿瘤(P = 0.0009),低级别浆液性肿瘤(P<0.0001)和高级别浆液性癌(P = 0.0036)中,与间质相比,类固醇激素受体在上皮细胞中表现出更强的表达。相反,在黏液性肿瘤,较之于上皮,间质中有更强的表达(P<0.0001)。这可能是由于他们不是来自于苗勒上皮。总之,我们的研究结果强烈支持这一观点:卵巢上皮性肿瘤周围的间质被激活,释放类固醇激素,后者可能进一步刺激肿瘤生长。这个过程发生的确切机制可能是复杂的,需要进一步研究。

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