Synchronous primary endometrial and ovarian cancers (SEOs) represent 10% of all endometrial and ovarian cancers and are assumed to develop as independent entities. We investigated the clonal relationship between endometrial and ovarian carcinomas in a large cohort classified as SEOs or metastatic disease (MD). The molecular profiles were compared to The Cancer Genome Atlas (TCGA) data to explore primary origin. Subsequently, the molecular profiles were correlated with clinical outcome. To this extent, a retrospective multicenter study was performed comparing patients with SEOs (n = 50), endometrial cancer with synchronous ovarian metastasis (n = 19) and ovarian cancer with synchronous endometrial metastasis (n = 20). Targeted next-generation sequencing was used, and a clonality index was calculated. Subsequently, cases were classified as POLE mutated, mismatch repair deficient (MMR-D), TP53-wild-type or TP53-mutated. In 92% of SEOs (46/50), the endometrial and concurrent ovarian carcinoma shared at least one somatic mutation, with a clonality index above 0.95, supporting a clonal origin. The SEO molecular profiles showed striking similarities with the TCGA endometrial carcinoma set. SEOs behaved distinctly different from metastatic disease, with a superior outcome compared to endometrial MD cases (p < 0.001) and ovarian MD cases (p < 0.001). Classification according to the TCGA identified four groups with different clinical outcomes. TP53 mutations and extra-utero-ovarian disease were independent predictors for poor clinical outcome. Concluding, SEOs were clonally related in an overwhelming majority of cases and showed a favorable prognosis. Their molecular profile implied a primary endometrial origin. TP53 mutation and extra-utero-ovarian disease were independent predictors for outcome, and may impact adjuvant systemic treatment planning.

中文翻译：

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分子谱分析将同步性子宫内膜癌和卵巢癌确定为转移性子宫内膜癌，具有良好的临床效果。

同步原发性子宫内膜癌和卵巢癌（SEO）占所有子宫内膜癌和卵巢癌的10％，并假定会发展为独立实体。我们调查了分类为SEO或转移性疾病（MD）的大型队列中子宫内膜癌与卵巢癌之间的克隆关系。将分子概况与《癌症基因组图谱》（TCGA）数据进行比较，以探索主要来源。随后，将分子概况与临床结果相关联。在这个程度上，进行了一项回顾性多中心研究，比较了SEOs（n = 50），子宫内膜癌伴有卵巢同步转移（n = 19）和卵巢癌伴子宫内膜转移（n = 20）的患者。使用靶向的下一代测序，并计算克隆指数。后来，病例分类为POLE突变，错配修复缺陷（MMR-D），TP53野生型或TP53突变。在92％的SEO中（46/50），子宫内膜癌和并发卵巢癌共享至少一种体细胞突变，克隆指数高于0.95，支持克隆起源。SEO分子图谱显示与TCGA子宫内膜癌组惊人相似。SEO的行为与转移性疾病明显不同，与子宫内膜MD病例（p <0.001）和卵巢MD病例（p <0.001）相比，结果要好。根据TCGA的分类，确定了四组临床结果不同的组。TP53突变和子宫外卵巢疾病是不良临床预后的独立预测因子。最后，SEO在绝大多数情况下都与克隆相关，并且预后良好。它们的分子特征暗示了主要的子宫内膜起源。TP53突变和子宫外卵巢疾病是预后的独立预测因素，可能会影响辅助性全身治疗计划。