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Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer.

  • Author(s): Konecny, GE
  • Wang, C
  • Hamidi, H
  • Winterhoff, B
  • Kalli, KR
  • Dering, J
  • Ginther, C
  • Chen, HW
  • Dowdy, S
  • Cliby, W
  • Gostout, B
  • Podratz, KC
  • Keeney, G
  • Wang, HJ
  • Hartmann, LC
  • Slamon, DJ
  • Goode, EL
  • et al.
Abstract

Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confid ence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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