1. Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion
- Author
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Sarah Minner, Claudia Hube-Magg, Hartwig Huland, Doris Höflmayer, Eike Burandt, Jakob R. Izbicki, Stefan Steurer, Luisa Harms, Sören Weidemann, David Dum, Andreas M. Luebke, Franziska Büscheck, Thorsten Schlomm, Cornelia Schroeder, Alexander Haese, Guido Sauter, Katharina Möller, Christoph Fraune, Markus Graefen, Patrick Lebok, Maria Christina Tsourlakis, Hans Heinzer, Simon Kind, Till S. Clauditz, Ronald Simon, and Christina Möller-Koop
- Subjects
0301 basic medicine ,Male ,Oncogene Proteins, Fusion ,Prostate cancer ,0302 clinical medicine ,Prostate ,Medicine ,lcsh:QD415-436 ,TFAP2D ,Genetics (clinical) ,Aged, 80 and over ,Tissue microarray ,Margins of Excision ,Middle Aged ,prostate cancer ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,immunohistochemistry ,Molecular Medicine ,Immunohistochemistry ,Chromosome Deletion ,Erg ,Research Article ,Adult ,TMPRSS2 ,lcsh:Biochemistry ,03 medical and health sciences ,Genetics ,Humans ,tissue micro array ,Molecular Biology ,Aged ,Neoplasm Staging ,business.industry ,Gene Expression Profiling ,lcsh:RM1-950 ,Prostatic Neoplasms ,medicine.disease ,genomic instability ,Molecular medicine ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Transcription Factor AP-2 ,Tissue Array Analysis ,Cancer research ,prognosis ,business ,Immunostaining - Abstract
Background TFAP2D is a transcription factor important for modulating gene expression in embryogenesis. Its expression and prognostic role in prostate cancer has not been evaluated. Methods Therefore, 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. Results TFAP2D 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 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. Conclusion These data demonstrate that TFAP2D protein overexpression is linked to prostate cancer progression and genomic instability in ERG negative prostate cancers.
- Published
- 2020
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