title: TFAP2C expression in breast cancer: correlation with overall survival beyond 10 years of initial diagnosis.
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.
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Perkins
authors.forename: Casey
authors.initials: C
authors.lastname: Bales
authors.forename: Tudor
authors.initials: T
authors.lastname: Vladislav
authors.forename: Sandra
authors.initials: S
authors.lastname: Althouse
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.forename: George
authors.initials: G
authors.lastname: Sandusky
authors.forename: Sunil
authors.initials: S
authors.lastname: Badve
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Nakshatri
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D016016:Proportional Hazards Models; D016019:Survival Analysis; D046888:Tissue Array Analysis; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2