title: Expression of steroid receptor coactivator 3 in ovarian epithelial cancer is a poor prognostic factor and a marker for platinum resistance.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Molecular and Clinical Cancer Medicine, Institute of translational Medicine, University of Liverpool,Liverpool, UK. c.palmieri@liverpool.ac.uk
authors: C
authors: C
authors: Palmieri
authors: O
authors: O
authors: Gojis
authors: B
authors: B
authors: Rudraraju
authors: C
authors: C
authors: Stamp-Vincent
authors: D
authors: D
authors: Wilson
authors: S
authors: S
authors: Langdon
authors: C
authors: C
authors: Gourley
authors: D
authors: D
authors: Faratian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism / Q000502:physiology; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D017671:Platinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D017671:Platinum Compounds; D043823:Taxoids; D056921:Nuclear Receptor Coactivator 3
references: J Clin Oncol. 1993 Oct;11(10):1957-68
references: 7691999
references: Histopathology. 2008 Jun;52(7):847-55
references: 18494613
references: Gynecol Oncol. 1996 Jul;62(1):4-6
references: 8690289
references: Cancer. 1991 Jul 15;68(2):269-71
references: 2070324
references: Gynecol Oncol. 2003 Dec;91(3):596-602
references: 14675683
references: Int J Gynecol Cancer. 2011 May;21(4):756-62
references: 21543937
references: Cancer Res. 2004 Nov 15;64(22):8299-308
references: 15548698
references: Cancer Epidemiol Biomarkers Prev. 2005 Dec;14(12):2919-22
references: 16365010
references: Lancet. 2002 Aug 17;360(9332):505-15
references: 12241653
references: Eur J Cancer. 1994;30A(5):682-6
references: 8080688
references: Cancer Res. 2009 Apr 1;69(7):2996-3003
references: 19318572
references: J Steroid Biochem Mol Biol. 1994 Aug;50(3-4):131-5
references: 8049141
references: J Vis Exp. 2011 Oct 25;(56):e3334
references: 22064683
references: Int J Cancer. 1993 Sep 30;55(3):459-64
references: 8375930
references: Eur J Cancer. 2011 Jun;47(9):1420-31
references: 21334202
references: Clin Cancer Res. 2002 Jul;8(7):2233-9
references: 12114425
references: Clin Cancer Res. 2007 Mar 1;13(5):1405-11
references: 17332282
references: Clin Cancer Res. 1998 Sep;4(9):2245-51
references: 9748145
references: Mol Cell Biol. 2008 Apr;28(7):2460-9
references: 18212051
references: J Clin Oncol. 2000 Jan;18(1):106-15
references: 10623700
references: J Natl Cancer Inst. 1994 Jun 1;86(11):829-35
references: 8182763
references: J Natl Cancer Inst. 2003 Mar 5;95(5):353-61
references: 12618500
references: Breast Cancer Res Treat. 2008 May;109(2):255-62
references: 17636398
references: Ann Oncol. 2010 Feb;21(2):238-244
references: 19628566
references: Clin Cancer Res. 2007 Jun 15;13(12):3617-22
references: 17575226
references: Cancer Lett. 2008 Mar 8;261(1):64-73
references: 18162290
references: Clin Cancer Res. 2000 May;6(5):1833-9
references: 10815905
references: Nature. 2008 Dec 4;456(7222):663-6
references: 19005469
references: Clin Cancer Res. 2004 Nov 1;10(21):7252-9
references: 15534099
references: Br J Cancer. 1990 Aug;62(2):213-6
references: 2386737
references: Oncology. 2004;66(2):112-7
references: 15138362
references: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1339-44
references: 15677324
references: Nat Rev Clin Oncol. 2010 Feb;7(2):83-9
references: 20027190
references: Eur J Surg Oncol. 2010 Mar;36(3):224-9
references: 19716257
references: Cell. 2000 Dec 22;103(7):1047-58
references: 11163181
references: Mol Cell Biol. 2008 Oct;28(19):5937-50
references: 18644862
references: Mol Cell. 2008 Sep 26;31(6):835-49
references: 18922467