Are Epithelial Ovarian Cancers of the Mesenchymal Subtype Actually Intraperitoneal Metastases to the Ovary?
Are Epithelial Ovarian Cancers of the Mesenchymal Subtype Actually Intraperitoneal Metastases to the Ovary?
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DOI：
10.3389/fcell.2020.00647
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发表时间：
2020-07-17
影响因子：
5.5
通讯作者：
Orsulic, Sandra
中科院分区：
文献类型：
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作者：
Hu, Ye;Taylor-Harding, Barbie;Orsulic, Sandra
原发性卵巢高级别浆液性癌（HGSC）被分为免疫反应性、增生性、分化性和间充质（Mes） 4种分子亚型，其中Mes亚型（Mes-HGSC）与最差的临床结果相关。我们认为Mes-HGSC由肿瘤簇和相关基质细胞组成，这些细胞从上腹部/大网膜的肿瘤中分离出来，并播散到腹腔，包括卵巢。通过对多个转录组数据集的比较分析，我们提供了以下证据，证明Mes-HGSC的表型与上腹部/大网膜肿瘤的表型相匹配：(1)无论卵巢HGSC的原发分子亚型如何，匹配的上腹部/大网膜转移灶通常为Mes亚型；(2)Mes亚型仅在同时发生上腹部/大网膜转移的患者中出现在卵巢部位，而局限于卵巢的HGSC患者中没有；(3)卵巢Mes-HGSC具有上腹部/大网膜转移灶间质细胞的表达谱特征。我们认为卵巢Mes-HGSC表明晚期腹腔内肿瘤播散到卵巢，而不是原发性卵巢HGSC的亚型。这与先前报道的与其他分子亚型相比，卵巢Mes-HGSC患者存在上腹部/大网膜疾病、次优减积和最差生存率一致。
Primary ovarian high-grade serous carcinoma (HGSC) has been classified into 4 molecular subtypes: Immunoreactive, Proliferative, Differentiated, and Mesenchymal (Mes), of which the Mes subtype (Mes-HGSC) is associated with the worst clinical outcomes. We propose that Mes-HGSC comprise clusters of cancer and associated stromal cells that detached from tumors in the upper abdomen/omentum and disseminated in the peritoneal cavity, including to the ovary. Using comparative analyses of multiple transcriptomic data sets, we provide the following evidence that the phenotype of Mes-HGSC matches the phenotype of tumors in the upper abdomen/omentum: (1) irrespective of the primary ovarian HGSC molecular subtype, matched upper abdominal/omental metastases were typically of the Mes subtype, (2) the Mes subtype was present at the ovarian site only in patients with concurrent upper abdominal/omental metastases and not in those with HGSC confined to the ovary, and (3) ovarian Mes-HGSC had an expression profile characteristic of stromal cells in the upper abdominal/omental metastases. We suggest that ovarian Mes-HGSC signifies advanced intraperitoneal tumor dissemination to the ovary rather than a subtype of primary ovarian HGSC. This is consistent with the presence of upper abdominal/omental disease, suboptimal debulking, and worst survival previously reported in patients with ovarian Mes-HGSC compared to other molecular subtypes.