Are Epithelial Ovarian Cancers of the Mesenchymal Subtype Actually Intraperitoneal Metastases to the Ovary?

Ye Hu, Barbie Taylor-Harding, Yael Raz, Marcela Haro, Maria Sol Recouvreux, Enes Taylan, Jenny Lester, Joshua Millstein, Ann E. Walts, Beth Y. Karlan, Sandra Orsulic

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number647
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
StatePublished - Jul 17 2020
Externally publishedYes

Keywords

  • desmoplasia
  • mesenchymal
  • metastases
  • molecular subtype
  • ovarian cancer

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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