Abstract
BackgroundTFAP2D is a transcription factor important for modulating gene expression in embryogenesis. Its expression and prognostic role in prostate cancer has not been evaluated.MethodsTherefore, a tissue microarray containing 17,747 prostate cancer specimens with associated pathological, clinical, and molecular data was analyzed by immunohistochemistry to assess the role of TFAP2D.ResultsTFAP2D expression was typically increased in prostate cancer as compared to adjacent non-neoplastic glands. TFAP2D staining was considered negative in 24.3% and positive in 75.7% of 13,545 interpretable cancers. TFAP2D staining was significantly linked to advanced tumor stage, high classical and quantitative Gleason grade, lymph node metastasis, and a positive surgical margin (p ≤ 0.0045). TFAP2D positivity was more common in ERG fusion positive (88.7%) than in ERG negative cancers (66.8%; p < 0.0001). Subset analyses in 3776 cancers with and 4722 cancers without TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. Multivariate analysis did not identify TFAP2D protein expression levels as a robust independent prognostic parameter. Positive TFAP2D immunostaining was significantly associated with 10 of 11 previously analyzed chromosomal deletions in ERG negative cancers (p ≤ 0.0244 each) indicating that elevated TFAP2D expression parallels genomic instability in prostate cancer.ConclusionThese data demonstrate that TFAP2D protein overexpression is linked to prostate cancer progression and genomic instability in ERG negative prostate cancers.
Highlights
Prostate cancer is the most prevalent cancer in men in developed countries and is clinically characterized by a broad spectrum of tumor phenotype from incidentally discovered and clinically silent tumors to highly aggressive and metastasizing tumors with significant mortality (Bray et al 2018)
The transcription factor AP-2 family consists of five isoforms (AP-2α to AP-2ε) that modulate gene expression after dimerization via binding to palindromic GCrich sequences in promotor and enhancer regions of various genes that impart cellular proliferation and differentiation (Eckert et al 2005; Williams and Tjian 1991)
Based on the reported role of Transcriptions factor AP2δ (TFAP2D) in prostate tissue and the implications of AP-2 family members in neoplasia (Cheng et al 2002), we aimed to determine the potential role of varying TFAP2D expression levels in prostate cancer
Summary
Prostate cancer is the most prevalent cancer in men in developed countries and is clinically characterized by a broad spectrum of tumor phenotype from incidentally discovered and clinically silent tumors to highly aggressive and metastasizing tumors with significant mortality (Bray et al 2018). Clinical parameters such as serum PSA-levels as well as histopathologic criteria, especially Gleason tumor grading, are widely used. These methods may lack reliable prediction of disease course in individual cases. The transcription factor AP-2 family consists of five isoforms (AP-2α to AP-2ε) that modulate gene expression after dimerization via binding to palindromic GCrich sequences in promotor and enhancer regions of various genes that impart cellular proliferation and differentiation (Eckert et al 2005; Williams and Tjian 1991). Its expression and prognostic role in prostate cancer has not been evaluated
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