TFAP2C expression in breast cancer: correlation with overall survival beyond 10 years of initial diagnosis

Breast Cancer Res Treat. 2015 Aug;152(3):519-31. doi: 10.1007/s10549-015-3492-2. Epub 2015 Jul 10.

Abstract

Recurrence and death in a significant number of patients with ERα-positive breast cancer occurs 10-20 years after diagnosis. Prognostic markers for late events have been more elusive. TFAP2C (AP2γ) regulates the expression of ERα, the ERα pioneer factors FOXA1 and GATA3, and controls ERα-dependent transcription. The purpose of this investigation is to determine the long-term prognostic value of TFAP2C. A tissue microarray (TMA) consisting of breast tumors from 451 patients with median follow-up time of 10.3 years was created and tested for the expression of TFAP2C by immunohistochemistry. Wilcoxon Rank-Sum and Kruskal-Wallis tests were used to determine if TFAP2C H-scores correlate with other tumor markers. Cox proportional hazards regression models were used to determine whether TFAP2C H-scores and other tumor markers were related to overall and disease-free survival in univariate and multivariable models. TFPAC2 overexpression did not impact overall survival during the first 10 years after diagnosis, but was associated with a shorter survival after 10 years (HR 3.40, 95 % CI 1.58, 7.30; p value = 0.002). This late divergence persisted in ER-positive (HR 2.86, 95 % CI 1.29, 6.36; p value = 0.01) and endocrine therapy-positive subgroups (HR 4.19, 95 % CI 1.72, 10.23; p value = 0.002). For the ER+ and endocrine therapy subgroup, the HR was 3.82 (95 % CI 1.53, 9.50; p value = 0.004). TFAP2C H-scores were not correlated with other tumor markers or related to disease-free survival. In this hypothesis-generating study, we show that higher TFAP2C scores correlate with poor overall survival after 10 years of diagnosis in ERα-positive and endocrine therapy-treated subgroups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Disease-Free Survival
  • Estrogen Receptor alpha / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Proportional Hazards Models
  • Survival Analysis
  • Tissue Array Analysis
  • Transcription Factor AP-2 / genetics
  • Transcription Factor AP-2 / metabolism*

Substances

  • Biomarkers, Tumor
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • TFAP2C protein, human
  • Transcription Factor AP-2