The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer
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The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer. / Büscheck, Franziska; Zub, Maciej; Heumann, Asmus; Hube-Magg, Claudia; Simon, Ronald; Lang, Dagmar S; Höflmayer, Doris; Neubauer, Emily; Jacobsen, Frank; Hinsch, Andrea; Luebke, Andreas M; Tsourlakis, Maria Christina; Sauter, Guido; Huland, Hartwig; Graefen, Markus; Haese, Alexander; Heinzer, Hans; Schlomm, Torsten; Clauditz, Till S; Burandt, Eike; Wilczak, Waldemar; Steurer, Stefan; Minner, Sarah.
in: TUMOR BIOL, Jahrgang 41, Nr. 7, 07.2019, S. 1010428318824815.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The independent prognostic impact of the GATA2 pioneering factor is restricted to ERG-negative prostate cancer
AU - Büscheck, Franziska
AU - Zub, Maciej
AU - Heumann, Asmus
AU - Hube-Magg, Claudia
AU - Simon, Ronald
AU - Lang, Dagmar S
AU - Höflmayer, Doris
AU - Neubauer, Emily
AU - Jacobsen, Frank
AU - Hinsch, Andrea
AU - Luebke, Andreas M
AU - Tsourlakis, Maria Christina
AU - Sauter, Guido
AU - Huland, Hartwig
AU - Graefen, Markus
AU - Haese, Alexander
AU - Heinzer, Hans
AU - Schlomm, Torsten
AU - Clauditz, Till S
AU - Burandt, Eike
AU - Wilczak, Waldemar
AU - Steurer, Stefan
AU - Minner, Sarah
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Disease Progression
KW - Disease-Free Survival
KW - Follow-Up Studies
KW - GATA2 Transcription Factor/metabolism
KW - Humans
KW - Kaplan-Meier Estimate
KW - Lymphatic Metastasis
KW - Male
KW - Middle Aged
KW - Multivariate Analysis
KW - Neoplasm Invasiveness
KW - Neoplasm Recurrence, Local
KW - Phenotype
KW - Prognosis
KW - Prostatectomy
KW - Prostatic Neoplasms/diagnosis
KW - Receptors, Androgen/metabolism
KW - Tissue Array Analysis
KW - Transcriptional Regulator ERG/metabolism
KW - Treatment Outcome
U2 - 10.1177/1010428318824815
DO - 10.1177/1010428318824815
M3 - SCORING: Journal article
C2 - 31296150
VL - 41
SP - 1010428318824815
JO - TUMOR BIOL
JF - TUMOR BIOL
SN - 1010-4283
IS - 7
ER -