The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer

GATA2 is a pioneering transcription factor governing androgen receptor expression and signaling in prostate cells. To understand the prognostic potential of GATA2 assessment in prostate cancer, we analyzed nuclear GATA2 expression on an annotated tissue microarray with 12,427 prostate cancer samples...

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Main Authors: Franziska Büscheck, Maciej Zub, Asmus Heumann, Claudia Hube-Magg, Ronald Simon, Dagmar S Lang, Doris Höflmayer, Emily Neubauer, Frank Jacobsen, Andrea Hinsch, Andreas M Luebke, Maria Christina Tsourlakis, Guido Sauter, Hartwig Huland, Markus Graefen, Alexander Haese, Hans Heinzer, Torsten Schlomm, Till S Clauditz, Eike Burandt, Waldemar Wilczak, Stefan Steurer, Sarah Minner
Format: Article
Language:English
Published: SAGE Publishing 2019-07-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428318824815
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author Franziska Büscheck
Maciej Zub
Asmus Heumann
Claudia Hube-Magg
Ronald Simon
Dagmar S Lang
Doris Höflmayer
Emily Neubauer
Frank Jacobsen
Andrea Hinsch
Andreas M Luebke
Maria Christina Tsourlakis
Guido Sauter
Hartwig Huland
Markus Graefen
Alexander Haese
Hans Heinzer
Torsten Schlomm
Till S Clauditz
Eike Burandt
Waldemar Wilczak
Stefan Steurer
Sarah Minner
author_facet Franziska Büscheck
Maciej Zub
Asmus Heumann
Claudia Hube-Magg
Ronald Simon
Dagmar S Lang
Doris Höflmayer
Emily Neubauer
Frank Jacobsen
Andrea Hinsch
Andreas M Luebke
Maria Christina Tsourlakis
Guido Sauter
Hartwig Huland
Markus Graefen
Alexander Haese
Hans Heinzer
Torsten Schlomm
Till S Clauditz
Eike Burandt
Waldemar Wilczak
Stefan Steurer
Sarah Minner
author_sort Franziska Büscheck
collection DOAJ
description GATA2 is a pioneering transcription factor governing androgen receptor expression and signaling in prostate cells. To understand the prognostic potential of GATA2 assessment in prostate cancer, we analyzed nuclear GATA2 expression on an annotated tissue microarray with 12,427 prostate cancer samples. Normal prostate glands were negative to weakly positive. GATA2 staining was found in almost all prostate cancers (95%). Strong GATA2 staining was linked to advanced tumor stage, high classical and quantitative Gleason grade (p < 0.0001 each), positive nodal stage (p = 0.0116), and early biochemical recurrence (p < 0.0001). GATA2 was linked to ERG -fusion-type cancers, with strong GATA2 staining in 29% of ERG-negative and 53% of ERG-positive cancers (p < 0.0001). Separate calculations in 3854 cancers with and 4768 cancers without TMPRSS2:ERG fusion revealed that these associations with tumor phenotype and patient outcome were largely driven by the subset of ERG-negative tumors. GATA2 expression was further linked to androgen receptor expression: Only 8% of androgen receptor-negative, but 56% of strongly androgen receptor expressing cancers had strong GATA2 expression (p < 0.0001). In conclusion, the results of our study demonstrate that increasing GATA2 levels are linked to prostate cancer progression and aggressiveness. The prognostic value of GATA2 is remarkable in ERG-negative cancers. However, the upregulation of GATA2 in ERG-positive cancers makes it unsuitable as a prognostic marker in this patient subset.
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spelling doaj-art-cae2903c17d44a8db526b5e01a405e882025-08-20T02:54:47ZengSAGE PublishingTumor Biology1423-03802019-07-014110.1177/1010428318824815The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancerFranziska Büscheck0Maciej Zub1Asmus Heumann2Claudia Hube-Magg3Ronald Simon4Dagmar S Lang5Doris Höflmayer6Emily Neubauer7Frank Jacobsen8Andrea Hinsch9Andreas M Luebke10Maria Christina Tsourlakis11Guido Sauter12Hartwig Huland13Markus Graefen14Alexander Haese15Hans Heinzer16Torsten Schlomm17Till S Clauditz18Eike Burandt19Waldemar Wilczak20Stefan Steurer21Sarah Minner22Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyGeneral, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMartini-Clinic Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMartini-Clinic Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMartini-Clinic Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMartini-Clinic Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Urology, Charité—Universitätsmedizin Berlin, Berlin, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyGATA2 is a pioneering transcription factor governing androgen receptor expression and signaling in prostate cells. To understand the prognostic potential of GATA2 assessment in prostate cancer, we analyzed nuclear GATA2 expression on an annotated tissue microarray with 12,427 prostate cancer samples. Normal prostate glands were negative to weakly positive. GATA2 staining was found in almost all prostate cancers (95%). Strong GATA2 staining was linked to advanced tumor stage, high classical and quantitative Gleason grade (p < 0.0001 each), positive nodal stage (p = 0.0116), and early biochemical recurrence (p < 0.0001). GATA2 was linked to ERG -fusion-type cancers, with strong GATA2 staining in 29% of ERG-negative and 53% of ERG-positive cancers (p < 0.0001). Separate calculations in 3854 cancers with and 4768 cancers without TMPRSS2:ERG fusion revealed that these associations with tumor phenotype and patient outcome were largely driven by the subset of ERG-negative tumors. GATA2 expression was further linked to androgen receptor expression: Only 8% of androgen receptor-negative, but 56% of strongly androgen receptor expressing cancers had strong GATA2 expression (p < 0.0001). In conclusion, the results of our study demonstrate that increasing GATA2 levels are linked to prostate cancer progression and aggressiveness. The prognostic value of GATA2 is remarkable in ERG-negative cancers. However, the upregulation of GATA2 in ERG-positive cancers makes it unsuitable as a prognostic marker in this patient subset.https://doi.org/10.1177/1010428318824815
spellingShingle Franziska Büscheck
Maciej Zub
Asmus Heumann
Claudia Hube-Magg
Ronald Simon
Dagmar S Lang
Doris Höflmayer
Emily Neubauer
Frank Jacobsen
Andrea Hinsch
Andreas M Luebke
Maria Christina Tsourlakis
Guido Sauter
Hartwig Huland
Markus Graefen
Alexander Haese
Hans Heinzer
Torsten Schlomm
Till S Clauditz
Eike Burandt
Waldemar Wilczak
Stefan Steurer
Sarah Minner
The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer
Tumor Biology
title The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer
title_full The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer
title_fullStr The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer
title_full_unstemmed The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer
title_short The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer
title_sort independent prognostic impact of the gata2 pioneering factor is restricted to erg negative prostate cancer
url https://doi.org/10.1177/1010428318824815
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