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

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• 作者：Susan M. Perkins ; Casey Bales ; Tudor Vladislav…
• 关键词：TFAP2C ; Estrogen receptor ; Breast cancer ; Outcome
• 刊名：Breast Cancer Research and Treatment
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：152
• 期：3
• 页码：519-531
• 全文大小：6,830 KB
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• 作者单位：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)
  
  1. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
  2. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
  3. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
  4. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
  5. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, C218C, 980 West Walnut St., Indianapolis, IN, 46202, USA
  6. Richard L. Roudebush VA Medical Center, Indianapolis, IN, 46202, USA
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

Recurrence and death in a significant number of patients with ERα-positive breast cancer occurs 10-0?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.