Centre Hospitalier Universitaire de Québec (CHU de Québec) Research Center and Faculty of Pharmacy, Laval University, Québec, Canada.
Gynecologic Oncology Service, CHU de Québec, and Department of Obstetrics, Gynecology, and Reproduction, Faculty of Medicine, Laval University, Québec, Canada.
J Steroid Biochem Mol Biol. 2018 Apr;178:45-54. doi: 10.1016/j.jsbmb.2017.10.021. Epub 2017 Oct 29.
Endometrial cancer (EC) is the most common gynecologic malignancy prevailing after menopause. Defining steroid profiles may help predict the risk of recurrence after hysterectomy, which remains limited due to the lack of reliable markers. Adrenal precursors, androgens, parent estrogens and catechol estrogen metabolites were measured by mass spectrometry (MS) in preoperative serums and those collected one month after hysterectomy from 246 newly diagnosed postmenopausal EC cases. We also examined the associations between steroid hormones and EC status by including 110 healthy postmenopausal women. Steroid concentrations were analyzed in relation to clinicopathological features, recurrence and overall survival (OS). The mean follow-up time was 65.5 months and 26 patients experienced relapse after surgery for a recurrence incidence of 10.6% (6.4% Type I and 29.5% Type II). Recurrence and OS were related to a more aggressive disease but not linked to body mass index. Preoperative levels of estriol (E) and estrone-sulfate (E-S) were inversely associated with recurrence in a multivariate logistic regression analysis (Hazard ratios (HRs) of 0.31, P=0.039 and 3.01, P=0.024; respectively). All circulating steroids declined considerably after surgery almost reaching those of healthy women, except 4-methoxy-E (4MeO-E) for which postoperative levels increased by 35% and were associated to a 68% decreased risk of recurrence (HR=0.32, P=0.015). Women diagnosed with both histological types of EC present significantly higher levels of steroids, in support of their mitogenic effects. The estrogen precursor E-S, the anticancer metabolite 4MeO-E, and E that exert mixed antagonist and agonist estrogenic activities and immunological effects, are potential independent prognostic factors.
子宫内膜癌（EC）是绝经后最常见的妇科恶性肿瘤。定义类固醇特征可能有助于预测子宫切除术后的复发风险，但由于缺乏可靠的标志物，这种预测仍然有限。我们通过质谱（MS）测量了 246 例新诊断的绝经后 EC 病例术前和子宫切除术后一个月收集的血清中的肾上腺前体、雄激素、母代雌激素和儿茶酚雌激素代谢物，并检查了类固醇激素与 EC 状态之间的关系，包括 110 例健康绝经后妇女。分析了类固醇浓度与临床病理特征、复发和总生存（OS）的关系。平均随访时间为 65.5 个月，26 例患者在手术后复发，复发率为 10.6%（6.4%为 I 型，29.5%为 II 型）。复发和 OS 与侵袭性更强的疾病有关，但与体重指数无关。多变量逻辑回归分析显示，术前雌三醇（E）和雌酮硫酸盐（E-S）水平与复发呈负相关（危险比（HRs）分别为 0.31，P=0.039 和 3.01，P=0.024）。除 4-甲氧基-E（4MeO-E）外，所有循环类固醇在手术后都显著下降，几乎达到健康女性的水平，4MeO-E 术后水平增加了 35%，与复发风险降低 68%相关（HR=0.32，P=0.015）。同时患有两种组织学类型 EC 的女性类固醇水平明显更高，支持其有丝分裂作用。雌激素前体 E-S、抗癌代谢物 4MeO-E 和具有混合拮抗剂和激动剂雌激素活性和免疫作用的 E，是潜在的独立预后因素。
