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Research in Review

Novel Ovarian Cancer Subtypes Associated With Survival Outcomes Following Surgery

High-grade serous ovarian cancer can be categorized in five molecular subtypes associated with survival and surgical outcomes, according to research published in Clinical Cancer Research (August 2017;23[15]:4077-4085).

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Biological features of high-grade serous ovarian cancer tumors that are associated with survival and surgical outcomes are currently being researched. The role of molecular subtyping to further this cause has yet to be determined.

Chen Wang, PhD, department of health sciences research, Mayo Clinic (Rochester, MN), and colleagues conducted clinical research to assess whether molecular subtyping can identify new biological features of high-grade serous ovarian cancer tumors that correlate with survival and surgical outcomes. Researchers used consensus clustering of pooled mRNA expression data from approximately 2000 patients with such disease to identify and define molecular subtypes. The resulting classification system was subsequently applied to 381 patients in the Mayo Clinic with detailed survival and surgical outcome information available.

Researchers identified five molecular subtypes of high-grade serous ovarian cancer. Three subtypes from the pooled dataset were significantly concordant ( > 70%) with prior studies describing proliferative, mesenchymal, and immunoreactive tumors. Tumors previously described as differentiated type were categorized into two new types, one of which was termed “anti-mesenchymal” due to the presence of downregulated genes that were typically upregulated in the mesenchymal subtype.

The identified molecular subtypes strongly correlated with overall survival (P < .001) and with the rate of optimal surgical debulking ( ≤ 1 cm, P = 1.9E−4) in the pooled dataset.

In the stage III-C or IV patients at the Mayo Clinic, molecular subtypes were also associated with overall survival (P = .001) and the rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors compared with > 28% in other subtypes; P = .02).

Authors of the study concluded that high-grade serous ovarian cancer tumors may be categorized into five distinct molecular subtypes that are significantly associated with overall survival and the extent of residual disease following debulking surgery.

Additionally, authors noted that associated outcomes for mesenchymal tumors may offer neoadjuvant guidance for patients with such tumors. “Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions,” they wrote.—Zachary Bessette