Expression of steroid receptor coactivator 3 in ovarian epithelial cancer is a poor prognostic factor and a marker for platinum resistance

Br J Cancer. 2013 May 28;108(10):2039-44. doi: 10.1038/bjc.2013.199. Epub 2013 May 7.

Abstract

Background: Steroid receptor coactivator 3 (SRC3) is an important coactivator of a number of transcription factors and is associated with a poor outcome in numerous tumours. Steroid receptor coactivator 3 is amplified in 25% of epithelial ovarian cancers (EOCs) and its expression is higher in EOCs compared with non-malignant tissue. No data is currently available with regard to the expression of SRC-3 in EOC and its influence on outcome or the efficacy of treatment.

Methods: Immunohistochemistry was performed for SRC3, oestrogen receptor-α, HER2, PAX2 and PAR6, and protein expression was quantified using automated quantitative immunofluorescence (AQUA) in 471 EOCs treated between 1991 and 2006 with cytoreductive surgery followed by first-line treatment platinum-based therapy, with or without a taxane.

Results: Steroid receptor coactivator 3 expression was significantly associated with advanced stage and was an independent prognostic marker. High expression of SRC3 identified patients who have a significantly poorer survival with single-agent carboplatin chemotherapy, while with carboplatin/paclitaxel treatment such a difference was not seen.

Conclusion: Steroid receptor coactivator 3 is a poor prognostic factor in EOCs and appears to identify a population of patients who would benefit from the addition of taxanes to their chemotherapy regimen, due to intrinsic resistance to platinum therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Pharmacological* / metabolism
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / physiology
  • Carcinoma, Ovarian Epithelial
  • Cohort Studies
  • Drug Resistance, Neoplasm* / physiology
  • Female
  • Humans
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / mortality
  • Nuclear Receptor Coactivator 3 / metabolism
  • Nuclear Receptor Coactivator 3 / physiology*
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality
  • Platinum Compounds / administration & dosage
  • Platinum Compounds / therapeutic use*
  • Prognosis
  • Retrospective Studies
  • Taxoids / administration & dosage

Substances

  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • Platinum Compounds
  • Taxoids
  • Nuclear Receptor Coactivator 3