Estrogen receptor-alpha as a predictive biomarker in endometrioid endometrial cancer.
Estrogen receptor-alpha as a predictive biomarker in endometrioid endometrial cancer.
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DOI：
10.1016/j.ygyno.2016.03.006
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发表时间：
2016-05
影响因子：
4.7
通讯作者：
Suarez AA
中科院分区：
文献类型：
--
作者：
Backes FJ;Walker CJ;Goodfellow PJ;Hade EM;Agarwal G;Mutch D;Cohn DE;Suarez AA
我们试图验证雌激素受体α(ERα)表达的预后意义，并调查ESR1突变状态与大量子宫内膜癌患者预后的关系。我们还研究了ER-α对大手术分期队列中淋巴结转移的预测价值。构建了仅包括单纯子宫内膜样腺癌的肿瘤微阵列(TMA)，用ER50单抗进行染色，并用数字图像分析进行评估。为了进行突变分析，提取了体细胞DNA并对ESR1基因热点区域进行了测序。比较ER-α阳性与阴性、突变与野生型肿瘤在患者及肿瘤特征、复发及生存率方面的差异。ER-α阴性60例(18.6%)。ERα缺失与肿瘤的分期和分级显著相关，但与无病生存或总生存期无关。ER-α是淋巴结转移的预测因子(RR：2.37，95%CI：1.12-5.02)。1034例肿瘤中有19例(1.8%)存在ESR1热点突变，其中12例位于537Y，4例位于538D，3例位于536L。ESR1突变患者的BMI显著较低，但在年龄、分期和分级以及无进展生存期方面相似。ERα阴性的子宫内膜样癌患者更容易被诊断为高级别和晚期疾病。在缺乏ERα表达的情况下，淋巴结受累更为常见，这可能有助于区分哪些患者应该接受淋巴清扫。ESR1的突变可能解释了为什么一些低BMI的低风险女性会患上子宫内膜癌。
We sought to validate the prognostic significance of Estrogen Receptor alpha (ERα) expression and to investigate the relationship between ESR1 mutation status and outcomes in a large cohort of patients with endometrial cancer. We also investigated the predictive value of ERα for lymph node involvement in a large surgically staged cohort. A tumor microarray (TMA) was constructed including only pure endometrioid adenocarcinomas, stained with ER50 monoclonal antibody, and assessed using digital image analysis. For mutation analysis, somatic DNA was extracted and sequenced for ESR1 gene hotspot regions. Differences in patient and tumor characteristics, recurrence and survival between ERα positive and negative, mutated and wild-type tumors were evaluated. Sixty (18.6%) tumors were negative for ERα. Absence of ERα was significantly associated with stage and grade, but not with disease-free or overall survival. ERα was a strong predictor of lymph node involvement (RR: 2.37, 95% CI: 1.12–5.02). Nineteen of 1034 tumors (1.8%) had an ESR1 hotspot mutation; twelve in hotspot 537Y, four in 538D and three in 536L. Patients with an ESR1 mutation had a significantly lower BMI, but were comparable in age, stage and grade, and progression-free survival. Patients with ERα negative endometrioid endometrial cancer are more often diagnosed with higher grade and advanced stage disease. Lymph node involvement is more common with lack of ERα expression, and may be able to help triage which patients should undergo lymphadenectomy. Mutations in ESR1 might explain why some low risk women with low BMI develop endometrial cancer.