Blanco Luis Z, Kuhn Elisabetta, Morrison Jane C, Bahadirli-Talbott Asli, Smith-Sehdev Anne, Kurman Robert J
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Department of Pathology, Legacy Health Systems, Portland, OR, USA.
Mod Pathol. 2017 Apr;30(4):563-576. doi: 10.1038/modpathol.2016.219. Epub 2017 Jan 6.
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.
上皮性卵巢肿瘤对甾体激素刺激有反应，卵巢基质可能在此过程中起直接作用。我们评估了101例上皮性卵巢肿瘤以及与卵巢癌发生相关的正常结构（卵巢表面上皮和皮质包涵囊肿）中性甾体分化和甾体生成的免疫组化标志物（钙视网膜蛋白、抑制素、甾体生成因子1）、参与激素生物合成的甾体酶（CYP17、CYP19、HSD17β1、AKR1C3）以及激素受体（雌激素受体、孕激素受体和雄激素受体），以试图阐明这一过程。我们假设紧邻肿瘤的卵巢基质表达性甾体分化和甾体生成的标志物以及甾体酶，而上皮含有相应的激素受体。由于浆液性、子宫内膜样和透明细胞肿瘤以及与子宫内膜异位症密切相关的肿瘤的结果非常相似，因此将它们合并为一组，称为“子宫内膜异位症相关肿瘤”。与较远的卵巢基质相比，紧邻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结果相似而合并）（P < 0.0001）的基质中性甾体分化和甾体生成标志物的表达显著增加。此外，与较远的基质相比，紧邻子宫内膜异位症相关肿瘤（P = 0.02）和黏液性肿瘤（P = 0.02）的基质中甾体激素酶增加。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，甾体激素受体在上皮中的表达高于基质。相比之下，黏液性肿瘤中基质中的表达高于上皮（P < 0.0001），这可能是因为它们并非源自苗勒上皮。总之，我们的研究结果有力地支持了这样一种观点，即卵巢上皮肿瘤周围的基质被激活以合成甾体激素，这可能会刺激肿瘤进一步生长。这一过程可能发生的精确机制很复杂，需要进一步研究。
