Research ExplorerPublicationsNuclear up regulation of the BRCA1-associated ubiquitinase B...

Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion

Standard

Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion. / Steurer, Stefan; Schwemmer, Lara; Hube-Magg, Claudia; Büscheck, Franziska; Höflmayer, Doris; Tsourlakis, Maria Christina; Clauditz, Till S; Luebke, Andreas M; Simon, Ronald; Sauter, Guido; Izbicki, Jakob; Schroeder, Cornelia; Schlomm, Thorsten; Huland, Hartwig; Heinzer, Hans; Haese, Alexander; Graefen, Markus; Göbel, Cosima; Weidemann, Sören; Lebok, Patrick; Dum, David; Fraune, Christoph; Minner, Sarah; Meiners, Jan.

In: ONCOTARGET, Vol. 10, No. 67, 24.12.2019, p. 7096-7111.

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

Harvard

Steurer, S, Schwemmer, L, Hube-Magg, C, Büscheck, F, Höflmayer, D, Tsourlakis, MC, Clauditz, TS, Luebke, AM, Simon, R, Sauter, G, Izbicki, J, Schroeder, C, Schlomm, T, Huland, H, Heinzer, H, Haese, A, Graefen, M, Göbel, C, Weidemann, S, Lebok, P, Dum, D, Fraune, C, Minner, S & Meiners, J 2019, 'Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion', ONCOTARGET, vol. 10, no. 67, pp. 7096-7111. https://doi.org/10.18632/oncotarget.27270

APA

Steurer, S., Schwemmer, L., Hube-Magg, C., Büscheck, F., Höflmayer, D., Tsourlakis, M. C., Clauditz, T. S., Luebke, A. M., Simon, R., Sauter, G., Izbicki, J., Schroeder, C., Schlomm, T., Huland, H., Heinzer, H., Haese, A., Graefen, M., Göbel, C., Weidemann, S., ... Meiners, J. (2019). Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion. ONCOTARGET, 10(67), 7096-7111. https://doi.org/10.18632/oncotarget.27270

Vancouver

Steurer S, Schwemmer L, Hube-Magg C, Büscheck F, Höflmayer D, Tsourlakis MC et al. Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion. ONCOTARGET. 2019 Dec 24;10(67):7096-7111. https://doi.org/10.18632/oncotarget.27270

Bibtex

@article{a135fac7afef4bd88124915717088679,
title = "Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion",
abstract = "Loss of the putative tumor suppressor BAP1 is a candidate biomarker for adverse prognosis in many cancer types, but conversely for improved survival in others. Studies on the expression and prognostic role of BAP1 in prostate cancer are currently lacking. We used a tissue microarray of 17,747 individual prostate cancer samples linked with comprehensive pathological, clinical and molecular data and studied the immunohistochemical expression of BAP1. BAP1 expression was typically up regulated in cancers as compared to adjacent normal prostatic glands. In 15,857 cancers, BAP1 staining was weak in 3.3%, moderate in 41.6% and strong in 17.4%. Strong BAP1 staining was associated with advanced tumor stage (p<0.0001), high classical and quantitative Gleason grade (p<0.0001), lymph node metastasis (p<0.0001), a positive surgical margin (p=0.0019) and early biochemical recurrence (p<0.0001). BAP1 expression was linked to ERG-fusion type cancers, with strong BAP1 staining in 12% of ERG-negative, but 30% of ERG-positive cancers (p<0.0001). Subset analyses in 5,415 cancers with and 4,217 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. Multivariate analysis revealed that the prognostic impact was independent of established prognostic features in ERG negative p<0.001) but not in ERG positive cancers. BAP1 expression was further linked to androgen receptor (AR) expression: Only 2% of AR-negative, but 33% of strongly AR expressing cancers had strong BAP1 expression (p<0.0001). In conclusion, this study shows that BAP1 up regulation is linked to prostate cancer progression and aggressiveness.",
author = "Stefan Steurer and Lara Schwemmer and Claudia Hube-Magg and Franziska B{\"u}scheck and Doris H{\"o}flmayer and Tsourlakis, {Maria Christina} and Clauditz, {Till S} and Luebke, {Andreas M} and Ronald Simon and Guido Sauter and Jakob Izbicki and Cornelia Schroeder and Thorsten Schlomm and Hartwig Huland and Hans Heinzer and Alexander Haese and Markus Graefen and Cosima G{\"o}bel and S{\"o}ren Weidemann and Patrick Lebok and David Dum and Christoph Fraune and Sarah Minner and Jan Meiners",
note = "Copyright: {\textcopyright} 2019 Steurer et al.",
year = "2019",
month = dec,
day = "24",
doi = "10.18632/oncotarget.27270",
language = "English",
volume = "10",
pages = "7096--7111",
journal = "ONCOTARGET",
issn = "1949-2553",
publisher = "IMPACT JOURNALS LLC",
number = "67",

}

RIS

TY - JOUR

T1 - Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion

AU - Steurer, Stefan

AU - Schwemmer, Lara

AU - Hube-Magg, Claudia

AU - Büscheck, Franziska

AU - Höflmayer, Doris

AU - Tsourlakis, Maria Christina

AU - Clauditz, Till S

AU - Luebke, Andreas M

AU - Simon, Ronald

AU - Sauter, Guido

AU - Izbicki, Jakob

AU - Schroeder, Cornelia

AU - Schlomm, Thorsten

AU - Huland, Hartwig

AU - Heinzer, Hans

AU - Haese, Alexander

AU - Graefen, Markus

AU - Göbel, Cosima

AU - Weidemann, Sören

AU - Lebok, Patrick

AU - Dum, David

AU - Fraune, Christoph

AU - Minner, Sarah

AU - Meiners, Jan

N1 - Copyright: © 2019 Steurer et al.

PY - 2019/12/24

Y1 - 2019/12/24

N2 - Loss of the putative tumor suppressor BAP1 is a candidate biomarker for adverse prognosis in many cancer types, but conversely for improved survival in others. Studies on the expression and prognostic role of BAP1 in prostate cancer are currently lacking. We used a tissue microarray of 17,747 individual prostate cancer samples linked with comprehensive pathological, clinical and molecular data and studied the immunohistochemical expression of BAP1. BAP1 expression was typically up regulated in cancers as compared to adjacent normal prostatic glands. In 15,857 cancers, BAP1 staining was weak in 3.3%, moderate in 41.6% and strong in 17.4%. Strong BAP1 staining was associated with advanced tumor stage (p<0.0001), high classical and quantitative Gleason grade (p<0.0001), lymph node metastasis (p<0.0001), a positive surgical margin (p=0.0019) and early biochemical recurrence (p<0.0001). BAP1 expression was linked to ERG-fusion type cancers, with strong BAP1 staining in 12% of ERG-negative, but 30% of ERG-positive cancers (p<0.0001). Subset analyses in 5,415 cancers with and 4,217 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. Multivariate analysis revealed that the prognostic impact was independent of established prognostic features in ERG negative p<0.001) but not in ERG positive cancers. BAP1 expression was further linked to androgen receptor (AR) expression: Only 2% of AR-negative, but 33% of strongly AR expressing cancers had strong BAP1 expression (p<0.0001). In conclusion, this study shows that BAP1 up regulation is linked to prostate cancer progression and aggressiveness.

AB - Loss of the putative tumor suppressor BAP1 is a candidate biomarker for adverse prognosis in many cancer types, but conversely for improved survival in others. Studies on the expression and prognostic role of BAP1 in prostate cancer are currently lacking. We used a tissue microarray of 17,747 individual prostate cancer samples linked with comprehensive pathological, clinical and molecular data and studied the immunohistochemical expression of BAP1. BAP1 expression was typically up regulated in cancers as compared to adjacent normal prostatic glands. In 15,857 cancers, BAP1 staining was weak in 3.3%, moderate in 41.6% and strong in 17.4%. Strong BAP1 staining was associated with advanced tumor stage (p<0.0001), high classical and quantitative Gleason grade (p<0.0001), lymph node metastasis (p<0.0001), a positive surgical margin (p=0.0019) and early biochemical recurrence (p<0.0001). BAP1 expression was linked to ERG-fusion type cancers, with strong BAP1 staining in 12% of ERG-negative, but 30% of ERG-positive cancers (p<0.0001). Subset analyses in 5,415 cancers with and 4,217 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. Multivariate analysis revealed that the prognostic impact was independent of established prognostic features in ERG negative p<0.001) but not in ERG positive cancers. BAP1 expression was further linked to androgen receptor (AR) expression: Only 2% of AR-negative, but 33% of strongly AR expressing cancers had strong BAP1 expression (p<0.0001). In conclusion, this study shows that BAP1 up regulation is linked to prostate cancer progression and aggressiveness.

U2 - 10.18632/oncotarget.27270

DO - 10.18632/oncotarget.27270

M3 - SCORING: Journal article

C2 - 31903168

VL - 10

SP - 7096

EP - 7111

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 67

ER -