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

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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.

in: MOL MED, Jahrgang 26, Nr. 1, 06.03.2020, S. 24.

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@article{d54586d6d91c41978ef70078423ab265,
title = "Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion",
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 < 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.",
author = "Christoph Fraune and Luisa Harms and Franziska B{\"u}scheck and Doris H{\"o}flmayer and Tsourlakis, {Maria Christina} and Clauditz, {Till S} and Ronald Simon and Katharina M{\"o}ller and Luebke, {Andreas M} and Christina M{\"o}ller-Koop and Stefan Steurer and Claudia Hube-Magg and Guido Sauter and S{\"o}ren Weidemann and Patrick Lebok and David Dum and Simon Kind and Sarah Minner and Izbicki, {Jakob R} and Thorsten Schlomm and Hartwig Huland and Hans Heinzer and Eike Burandt and Alexander Haese and Markus Graefen and Cornelia Schroeder",
year = "2020",
month = mar,
day = "6",
doi = "10.1186/s10020-020-00148-4",
language = "English",
volume = "26",
pages = "24",
journal = "MOL MED",
issn = "1076-1551",
publisher = "Feinstein Institute for Medical Research",
number = "1",

}

RIS

TY - JOUR

T1 - Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion

AU - Fraune, Christoph

AU - Harms, Luisa

AU - Büscheck, Franziska

AU - Höflmayer, Doris

AU - Tsourlakis, Maria Christina

AU - Clauditz, Till S

AU - Simon, Ronald

AU - Möller, Katharina

AU - Luebke, Andreas M

AU - Möller-Koop, Christina

AU - Steurer, Stefan

AU - Hube-Magg, Claudia

AU - Sauter, Guido

AU - Weidemann, Sören

AU - Lebok, Patrick

AU - Dum, David

AU - Kind, Simon

AU - Minner, Sarah

AU - Izbicki, Jakob R

AU - Schlomm, Thorsten

AU - Huland, Hartwig

AU - Heinzer, Hans

AU - Burandt, Eike

AU - Haese, Alexander

AU - Graefen, Markus

AU - Schroeder, Cornelia

PY - 2020/3/6

Y1 - 2020/3/6

N2 - 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.

AB - 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.

U2 - 10.1186/s10020-020-00148-4

DO - 10.1186/s10020-020-00148-4

M3 - SCORING: Journal article

C2 - 32143573

VL - 26

SP - 24

JO - MOL MED

JF - MOL MED

SN - 1076-1551

IS - 1

ER -