Overexpression of the TRIM24 E3 Ubiquitin Ligase is Linked to Genetic Instability and Predicts Unfavorable Prognosis in Prostate Cancer

TY - JOUR

T1 - Overexpression of the TRIM24 E3 Ubiquitin Ligase is Linked to Genetic Instability and Predicts Unfavorable Prognosis in Prostate Cancer

AU - Höflmayer, Doris

AU - Fraune, Christoph

AU - Hube-Magg, Claudia

AU - Simon, Ronald

AU - Schroeder, Cornelia

AU - Büscheck, Franziska

AU - Möller, Katharina

AU - Dum, David

AU - Weidemann, Sören

AU - Wittmer, Corinna

AU - Schlomm, Thorsten

AU - Huland, Hartwig

AU - Heinzer, Hans

AU - Graefen, Markus

AU - Haese, Alexander

AU - Sauter, Guido

AU - Burandt, Eike

AU - Clauditz, Till S

AU - Steurer, Stefan

AU - Minner, Sarah

AU - Wilczak, Waldemar

AU - Polonski, Adam

N1 - Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2021/4/1

Y1 - 2021/4/1

N2 - Tripartite motif containing 24 (TRIM24) is a multifunctional protein involved in p53 degradation, chromatin binding, and transcriptional modulation of nuclear receptors. Emerging research has revealed that upregulation of TRIM24 in numerous tumor types is linked to poor prognosis, attributing an important role to TRIM24 in tumor biology. In order to better understand the role of TRIM24 in prostate cancer, we analyzed its immunohistochemical expression on a tissue microarray containing >17,000 prostate cancer specimens. TRIM24 immunostaining was detectable in 61% of 15,321 interpretable cancers, including low expression in 46% and high expression in 15% of cases. TRIM24 upregulation was associated with high Gleason grade, advanced pathologic tumor stage, lymph node metastasis, higher preoperative prostate-specific antigen level, increased cell proliferation as well as increased genomic instability, and predicted prognosis independent of clinicopathologic parameters available at the time of the initial biopsy (all P<0.0001). TRIM24 upregulation provides additional prognostic information in prostate cancer, particularly in patients with low Gleason grade tumors who may be eligible for active surveillance strategies, suggesting promising potential for TRIM24 in the routine diagnostic work-up of these patients.

AB - Tripartite motif containing 24 (TRIM24) is a multifunctional protein involved in p53 degradation, chromatin binding, and transcriptional modulation of nuclear receptors. Emerging research has revealed that upregulation of TRIM24 in numerous tumor types is linked to poor prognosis, attributing an important role to TRIM24 in tumor biology. In order to better understand the role of TRIM24 in prostate cancer, we analyzed its immunohistochemical expression on a tissue microarray containing >17,000 prostate cancer specimens. TRIM24 immunostaining was detectable in 61% of 15,321 interpretable cancers, including low expression in 46% and high expression in 15% of cases. TRIM24 upregulation was associated with high Gleason grade, advanced pathologic tumor stage, lymph node metastasis, higher preoperative prostate-specific antigen level, increased cell proliferation as well as increased genomic instability, and predicted prognosis independent of clinicopathologic parameters available at the time of the initial biopsy (all P<0.0001). TRIM24 upregulation provides additional prognostic information in prostate cancer, particularly in patients with low Gleason grade tumors who may be eligible for active surveillance strategies, suggesting promising potential for TRIM24 in the routine diagnostic work-up of these patients.

U2 - 10.1097/PAI.0000000000000901

DO - 10.1097/PAI.0000000000000901

M3 - SCORING: Journal article

C2 - 33491944

VL - 29

SP - e29-e38

JO - APPL IMMUNOHISTO M M

JF - APPL IMMUNOHISTO M M

SN - 1541-2016

IS - 4

ER -