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Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion

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, clin...

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Autores principales: Fraune, Christoph, Harms, Luisa, Büscheck, Franziska, Höflmayer, Doris, Tsourlakis, Maria Christina, Clauditz, Till S., Simon, Ronald, Möller, Katharina, Luebke, Andreas M., Möller-Koop, Christina, Steurer, Stefan, Hube-Magg, Claudia, Sauter, Guido, Weidemann, Sören, Lebok, Patrick, Dum, David, Kind, Simon, Minner, Sarah, Izbicki, Jakob R., Schlomm, Thorsten, Huland, Hartwig, Heinzer, Hans, Burandt, Eike, Haese, Alexander, Graefen, Markus, Schroeder, Cornelia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060561/
https://www.ncbi.nlm.nih.gov/pubmed/32143573
http://dx.doi.org/10.1186/s10020-020-00148-4
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author Fraune, Christoph
Harms, Luisa
Büscheck, Franziska
Höflmayer, Doris
Tsourlakis, Maria Christina
Clauditz, Till S.
Simon, Ronald
Möller, Katharina
Luebke, Andreas M.
Möller-Koop, Christina
Steurer, Stefan
Hube-Magg, Claudia
Sauter, Guido
Weidemann, Sören
Lebok, Patrick
Dum, David
Kind, Simon
Minner, Sarah
Izbicki, Jakob R.
Schlomm, Thorsten
Huland, Hartwig
Heinzer, Hans
Burandt, Eike
Haese, Alexander
Graefen, Markus
Schroeder, Cornelia
author_facet Fraune, Christoph
Harms, Luisa
Büscheck, Franziska
Höflmayer, Doris
Tsourlakis, Maria Christina
Clauditz, Till S.
Simon, Ronald
Möller, Katharina
Luebke, Andreas M.
Möller-Koop, Christina
Steurer, Stefan
Hube-Magg, Claudia
Sauter, Guido
Weidemann, Sören
Lebok, Patrick
Dum, David
Kind, Simon
Minner, Sarah
Izbicki, Jakob R.
Schlomm, Thorsten
Huland, Hartwig
Heinzer, Hans
Burandt, Eike
Haese, Alexander
Graefen, Markus
Schroeder, Cornelia
author_sort Fraune, Christoph
collection PubMed
description 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 < 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. CONCLUSION: These data demonstrate that TFAP2D protein overexpression is linked to prostate cancer progression and genomic instability in ERG negative prostate cancers.
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spelling pubmed-70605612020-03-11 Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion Fraune, Christoph Harms, Luisa Büscheck, Franziska Höflmayer, Doris Tsourlakis, Maria Christina Clauditz, Till S. Simon, Ronald Möller, Katharina Luebke, Andreas M. Möller-Koop, Christina Steurer, Stefan Hube-Magg, Claudia Sauter, Guido Weidemann, Sören Lebok, Patrick Dum, David Kind, Simon Minner, Sarah Izbicki, Jakob R. Schlomm, Thorsten Huland, Hartwig Heinzer, Hans Burandt, Eike Haese, Alexander Graefen, Markus Schroeder, Cornelia Mol Med Research Article 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 < 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. CONCLUSION: These data demonstrate that TFAP2D protein overexpression is linked to prostate cancer progression and genomic instability in ERG negative prostate cancers. BioMed Central 2020-03-06 /pmc/articles/PMC7060561/ /pubmed/32143573 http://dx.doi.org/10.1186/s10020-020-00148-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Fraune, Christoph
Harms, Luisa
Büscheck, Franziska
Höflmayer, Doris
Tsourlakis, Maria Christina
Clauditz, Till S.
Simon, Ronald
Möller, Katharina
Luebke, Andreas M.
Möller-Koop, Christina
Steurer, Stefan
Hube-Magg, Claudia
Sauter, Guido
Weidemann, Sören
Lebok, Patrick
Dum, David
Kind, Simon
Minner, Sarah
Izbicki, Jakob R.
Schlomm, Thorsten
Huland, Hartwig
Heinzer, Hans
Burandt, Eike
Haese, Alexander
Graefen, Markus
Schroeder, Cornelia
Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion
title Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion
title_full Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion
title_fullStr Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion
title_full_unstemmed Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion
title_short Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion
title_sort upregulation of the transcription factor tfap2d is associated with aggressive tumor phenotype in prostate cancer lacking the tmprss2:erg fusion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060561/
https://www.ncbi.nlm.nih.gov/pubmed/32143573
http://dx.doi.org/10.1186/s10020-020-00148-4
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