Breast Cancer Research and Treatment

, Volume 152, Issue 3, pp 519–531 | Cite as

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

  • Susan M. Perkins
  • Casey Bales
  • Tudor Vladislav
  • Sandra Althouse
  • Kathy D. Miller
  • George Sandusky
  • Sunil Badve
  • Harikrishna NakshatriEmail author
Preclinical study


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.


TFAP2C Estrogen receptor Breast cancer Outcome 



We thank Janet Harlan and Jeanette Krohne for chart review, Lee Ann Baldridge for immunohistochemistry of TMA. IUPUI Signature center, IUSCC Breast Cancer Program, IUSCC Tissue Bank, and a grant from the Susan G. Komen for the Cure (SAC110025 to HN) supported this study.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Standards

The study was conducted in compliance with current laws of United States of America.

Supplementary material

10549_2015_3492_MOESM1_ESM.pdf (212 kb)
Supplementary material 1 (PDF 213 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Susan M. Perkins
    • 1
  • Casey Bales
    • 2
  • Tudor Vladislav
    • 3
  • Sandra Althouse
    • 1
  • Kathy D. Miller
    • 2
  • George Sandusky
    • 3
  • Sunil Badve
    • 3
  • Harikrishna Nakshatri
    • 4
    • 5
    • 6
    Email author
  1. 1.Department of BiostatisticsIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of MedicineIndiana University School of MedicineIndianapolisUSA
  3. 3.Department of Pathology and Laboratory MedicineIndiana University School of MedicineIndianapolisUSA
  4. 4.Department of SurgeryIndiana University School of MedicineIndianapolisUSA
  5. 5.Department of Biochemistry and Molecular BiologyIndiana University School of MedicineIndianapolisUSA
  6. 6.Richard L. Roudebush VA Medical CenterIndianapolisUSA

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