TLE3 expression is associated with sensitivity to taxane treatment in ovarian carcinoma

Cancer Epidemiol Biomarkers Prev. 2012 Feb;21(2):273-9. doi: 10.1158/1055-9965.EPI-11-0917. Epub 2011 Dec 22.

Abstract

Background: We have previously shown that transducin-like enhancer of split 3 (TLE3) is associated with outcome specifically in patients with taxane-treated breast cancer and not in patients treated with anthracycline-based regimens without a taxane. The purpose of this study was to assess the association between TLE3 expression and recurrence in patients with ovarian carcinoma treated with a taxane containing regimen as opposed to those treated with a platinum-based agent alone.

Methods: We carried out immunohistochemical staining of TLE3 in two series of ovarian cancer specimens from the University of Alabama at Birmingham, Birmingham, AL and the Royal Hospital for Women, Sydney, Australia. Local and distant recurrences within the first five years of follow-up were analyzed using Kaplan-Meier, Cox proportional hazard, and multivariate analysis to assess an association between TLE3 expression and response to therapy.

Results: TLE3 was expressed in approximately 30% of tumors and expression was associated with a favorable outcome only in patients who had received taxane as part of their treatment regimen (n = 173, HR = 0.62, P = 0.012; P(interaction) = 0.024). Further analysis revealed that the predictive association between TLE3 expression and outcome was strongest in patients with nonserous histology.

Conclusion: High TLE3 expression predicts a favorable response to taxane containing chemotherapy regimens in ovarian carcinoma.

Impact: Our findings warrant an independent evaluation of TLE3 as a potential therapeutic response marker for taxane-based chemotherapy in ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / biosynthesis
  • Bridged-Ring Compounds / administration & dosage
  • Bridged-Ring Compounds / therapeutic use*
  • Carcinoma, Ovarian Epithelial
  • Co-Repressor Proteins / biosynthesis*
  • Cohort Studies
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Multivariate Analysis
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Proportional Hazards Models
  • Taxoids / administration & dosage
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • Co-Repressor Proteins
  • TLE3 protein, human
  • Taxoids
  • taxane