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, Jahrgang 79, Nr. 3, 02.2019, S. 302-311.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -