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Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers

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Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers. / Minner, Sarah; Lutz, Jannes; Hube-Magg, Claudia; Kluth, Martina; Simon, Ronald; Höflmayer, Doris; Burandt, Eike; Tsourlakis, Maria Christina; Sauter, Guido; Büscheck, Franziska; Wilczak, Waldemar; Steurer, Stefan; Schlomm, Thorsten; Huland, Hartwig; Graefen, Markus; Haese, Alexander; Heinzer, Hans; Jacobsen, Frank; Hinsch, Andrea; Poos, Alexandra; Oswald, Marcus; Rippe, Karsten; König, Rainer; Schroeder, Cornelia.

In: PROSTATE, Vol. 79, No. 3, 02.2019, p. 302-311.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Minner, S, Lutz, J, Hube-Magg, C, Kluth, M, Simon, R, Höflmayer, D, Burandt, E, Tsourlakis, MC, Sauter, G, Büscheck, F, Wilczak, W, Steurer, S, Schlomm, T, Huland, H, Graefen, M, Haese, A, Heinzer, H, Jacobsen, F, Hinsch, A, Poos, A, Oswald, M, Rippe, K, König, R & Schroeder, C 2019, 'Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers', PROSTATE, vol. 79, no. 3, pp. 302-311. https://doi.org/10.1002/pros.23736

APA

Minner, S., Lutz, J., Hube-Magg, C., Kluth, M., Simon, R., Höflmayer, D., Burandt, E., Tsourlakis, M. C., Sauter, G., Büscheck, F., Wilczak, W., Steurer, S., Schlomm, T., Huland, H., Graefen, M., Haese, A., Heinzer, H., Jacobsen, F., Hinsch, A., ... Schroeder, C. (2019). Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers. PROSTATE, 79(3), 302-311. https://doi.org/10.1002/pros.23736

Vancouver

Minner S, Lutz J, Hube-Magg C, Kluth M, Simon R, Höflmayer D et al. Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers. PROSTATE. 2019 Feb;79(3):302-311. https://doi.org/10.1002/pros.23736

Bibtex

@article{a7bde0d3a7204577a9242bfe785850ce,
title = "Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers",
abstract = "BACKGROUND: The transcription factor CCAAT-enhancer-binding protein alpha (CEBPA) is a crucial regulator of cell proliferation and differentiation. Expression levels of CEBPA have been suggested to be prognostic in various tumor types.METHODS: Here, we analyzed the immunohistochemical expression of CEBPA in a tissue microarray containing more than 17 000 prostate cancer specimens with annotated clinical and molecular data including for example TMPRSS2:ERG fusion and PTEN deletion status.RESULTS: Normal prostate glands showed moderate to strong CEBPA staining, while CEBPA expression was frequently reduced (40%) or lost (30%) in prostate cancers. Absence of detectable CEBPA expression was markedly more frequent in ERG negative (45%) as compared to ERG positive cancers (20%, P < 0.0001). Reduced CEBPA expression was linked to unfavorable phenotype (P < 0.0001) and poor prognosis (P = 0.0008). Subgroup analyses revealed, that the prognostic value of CEBPA loss was entirely driven by tumors carrying both TMPRSS2:ERG fusions and PTEN deletions. In this subgroup, CEBPA loss was tightly linked to advanced tumor stage (P < 0.0001), high Gleason grade (P < 0.0001), positive nodal stage (0.0003), and early biochemical recurrence (P = 0.0007), while these associations were absent or markedly diminished in tumors with normal PTEN copy numbers and/or absence of ERG fusion.CONCLUSIONS: CEBPA is down regulated in about one third of prostate cancers, but the clinical impact of CEBPA loss is strictly limited to the subset of about 10% prostate cancers carrying both ERG fusion and deletions of the PTEN tumor suppressor. Our findings challenge the concept that prognostic molecular markers may be generally applicable to all prostate cancers.",
keywords = "Journal Article",
author = "Sarah Minner and Jannes Lutz and Claudia Hube-Magg and Martina Kluth and Ronald Simon and Doris H{\"o}flmayer and Eike Burandt and Tsourlakis, {Maria Christina} and Guido Sauter and Franziska B{\"u}scheck and Waldemar Wilczak and Stefan Steurer and Thorsten Schlomm and Hartwig Huland and Markus Graefen and Alexander Haese and Hans Heinzer and Frank Jacobsen and Andrea Hinsch and Alexandra Poos and Marcus Oswald and Karsten Rippe and Rainer K{\"o}nig and Cornelia Schroeder",
note = "{\textcopyright} 2018 Wiley Periodicals, Inc.",
year = "2019",
month = feb,
doi = "10.1002/pros.23736",
language = "English",
volume = "79",
pages = "302--311",
journal = "PROSTATE",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers

AU - Minner, Sarah

AU - Lutz, Jannes

AU - Hube-Magg, Claudia

AU - Kluth, Martina

AU - Simon, Ronald

AU - Höflmayer, Doris

AU - Burandt, Eike

AU - Tsourlakis, Maria Christina

AU - Sauter, Guido

AU - Büscheck, Franziska

AU - Wilczak, Waldemar

AU - Steurer, Stefan

AU - Schlomm, Thorsten

AU - Huland, Hartwig

AU - Graefen, Markus

AU - Haese, Alexander

AU - Heinzer, Hans

AU - Jacobsen, Frank

AU - Hinsch, Andrea

AU - Poos, Alexandra

AU - Oswald, Marcus

AU - Rippe, Karsten

AU - König, Rainer

AU - Schroeder, Cornelia

N1 - © 2018 Wiley Periodicals, Inc.

PY - 2019/2

Y1 - 2019/2

N2 - BACKGROUND: The transcription factor CCAAT-enhancer-binding protein alpha (CEBPA) is a crucial regulator of cell proliferation and differentiation. Expression levels of CEBPA have been suggested to be prognostic in various tumor types.METHODS: Here, we analyzed the immunohistochemical expression of CEBPA in a tissue microarray containing more than 17 000 prostate cancer specimens with annotated clinical and molecular data including for example TMPRSS2:ERG fusion and PTEN deletion status.RESULTS: Normal prostate glands showed moderate to strong CEBPA staining, while CEBPA expression was frequently reduced (40%) or lost (30%) in prostate cancers. Absence of detectable CEBPA expression was markedly more frequent in ERG negative (45%) as compared to ERG positive cancers (20%, P < 0.0001). Reduced CEBPA expression was linked to unfavorable phenotype (P < 0.0001) and poor prognosis (P = 0.0008). Subgroup analyses revealed, that the prognostic value of CEBPA loss was entirely driven by tumors carrying both TMPRSS2:ERG fusions and PTEN deletions. In this subgroup, CEBPA loss was tightly linked to advanced tumor stage (P < 0.0001), high Gleason grade (P < 0.0001), positive nodal stage (0.0003), and early biochemical recurrence (P = 0.0007), while these associations were absent or markedly diminished in tumors with normal PTEN copy numbers and/or absence of ERG fusion.CONCLUSIONS: CEBPA is down regulated in about one third of prostate cancers, but the clinical impact of CEBPA loss is strictly limited to the subset of about 10% prostate cancers carrying both ERG fusion and deletions of the PTEN tumor suppressor. Our findings challenge the concept that prognostic molecular markers may be generally applicable to all prostate cancers.

AB - BACKGROUND: The transcription factor CCAAT-enhancer-binding protein alpha (CEBPA) is a crucial regulator of cell proliferation and differentiation. Expression levels of CEBPA have been suggested to be prognostic in various tumor types.METHODS: Here, we analyzed the immunohistochemical expression of CEBPA in a tissue microarray containing more than 17 000 prostate cancer specimens with annotated clinical and molecular data including for example TMPRSS2:ERG fusion and PTEN deletion status.RESULTS: Normal prostate glands showed moderate to strong CEBPA staining, while CEBPA expression was frequently reduced (40%) or lost (30%) in prostate cancers. Absence of detectable CEBPA expression was markedly more frequent in ERG negative (45%) as compared to ERG positive cancers (20%, P < 0.0001). Reduced CEBPA expression was linked to unfavorable phenotype (P < 0.0001) and poor prognosis (P = 0.0008). Subgroup analyses revealed, that the prognostic value of CEBPA loss was entirely driven by tumors carrying both TMPRSS2:ERG fusions and PTEN deletions. In this subgroup, CEBPA loss was tightly linked to advanced tumor stage (P < 0.0001), high Gleason grade (P < 0.0001), positive nodal stage (0.0003), and early biochemical recurrence (P = 0.0007), while these associations were absent or markedly diminished in tumors with normal PTEN copy numbers and/or absence of ERG fusion.CONCLUSIONS: CEBPA is down regulated in about one third of prostate cancers, but the clinical impact of CEBPA loss is strictly limited to the subset of about 10% prostate cancers carrying both ERG fusion and deletions of the PTEN tumor suppressor. Our findings challenge the concept that prognostic molecular markers may be generally applicable to all prostate cancers.

KW - Journal Article

U2 - 10.1002/pros.23736

DO - 10.1002/pros.23736

M3 - SCORING: Journal article

C2 - 30430607

VL - 79

SP - 302

EP - 311

JO - PROSTATE

JF - PROSTATE

SN - 0270-4137

IS - 3

ER -