High-Level Glyoxalase 1 (GLO1) expression is linked to poor prognosis in prostate cancer
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High-Level Glyoxalase 1 (GLO1) expression is linked to poor prognosis in prostate cancer. / Burdelski, Christoph; Shihada, Rami; Hinsch, Andrea; Angerer, Alexander; Göbel, Cosima; Friedrich, Emily; Hube-Magg, Claudia; Burdak-Rothkamm, Susanne; Kluth, Martina; Simon, Ronald; Möller-Koop, Christina; Sauter, Guido; Büscheck, Franzika; Wittmer, Corinna; Clauditz, Till S; Krech, Till; Tsourlakis, Maria C; Minner, Sarah; Graefen, Markus; Schlomm, Thorsten; Wilczak, Waldemar; Jacobsen, Frank.
in: PROSTATE, Jahrgang 77, Nr. 15, 11.2017, S. 1528-1538.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - High-Level Glyoxalase 1 (GLO1) expression is linked to poor prognosis in prostate cancer
AU - Burdelski, Christoph
AU - Shihada, Rami
AU - Hinsch, Andrea
AU - Angerer, Alexander
AU - Göbel, Cosima
AU - Friedrich, Emily
AU - Hube-Magg, Claudia
AU - Burdak-Rothkamm, Susanne
AU - Kluth, Martina
AU - Simon, Ronald
AU - Möller-Koop, Christina
AU - Sauter, Guido
AU - Büscheck, Franzika
AU - Wittmer, Corinna
AU - Clauditz, Till S
AU - Krech, Till
AU - Tsourlakis, Maria C
AU - Minner, Sarah
AU - Graefen, Markus
AU - Schlomm, Thorsten
AU - Wilczak, Waldemar
AU - Jacobsen, Frank
N1 - © 2017 Wiley Periodicals, Inc.
PY - 2017/11
Y1 - 2017/11
N2 - BACKGROUND: Glyoxalase 1 (GLO1) is an enzyme involved in removal of toxic byproducts accumulating during glycolysis from the cell. GLO1 is up regulated in many cancer types but its role in prostate cancer is largely unknown.METHODS: Here, we employed GLO1 immunohistochemistry on a tissue microarray including 11 152 tumors and an attached clinical and molecular database.RESULTS: Normal prostate epithelium was negative for GLO1, whereas 2059 (27.3%) of 7552 interpretable cancers showed cytoplasmic GLO1 staining, which was considered weak in 8.8%, moderate in 12.5%, and strong in 6.1% of tumors. Up regulation of GLO1 was significantly linked to high original Gleason grade, advanced pathological tumor stage and positive lymph node status (P < 0.0001 each). Comparison of GLO1 staining with several common genomic alterations of prostate cancers revealed a strong link between GLO1 up regulation and TMPRSS2:ERG fusion (P < 0.0001) and an ERG-independent association with PTEN deletion (P < 0.0001). GLO1 up regulation was strongly linked to early biochemical recurrence in univariate analysis (P < 0.0001) and predicted poor prognosis independent from most (except from nodal stage) established prognostic parameters in multivariate analysis (P ≤ 0.03).CONCLUSIONS: GLO1 upregulation is linked to aggressive prostate cancers characterized by ERG fusion and PTEN deletion. The strong and independent prognostic value makes it a promising candidate for routine diagnostic applications either alone or in combination with other markers.
AB - BACKGROUND: Glyoxalase 1 (GLO1) is an enzyme involved in removal of toxic byproducts accumulating during glycolysis from the cell. GLO1 is up regulated in many cancer types but its role in prostate cancer is largely unknown.METHODS: Here, we employed GLO1 immunohistochemistry on a tissue microarray including 11 152 tumors and an attached clinical and molecular database.RESULTS: Normal prostate epithelium was negative for GLO1, whereas 2059 (27.3%) of 7552 interpretable cancers showed cytoplasmic GLO1 staining, which was considered weak in 8.8%, moderate in 12.5%, and strong in 6.1% of tumors. Up regulation of GLO1 was significantly linked to high original Gleason grade, advanced pathological tumor stage and positive lymph node status (P < 0.0001 each). Comparison of GLO1 staining with several common genomic alterations of prostate cancers revealed a strong link between GLO1 up regulation and TMPRSS2:ERG fusion (P < 0.0001) and an ERG-independent association with PTEN deletion (P < 0.0001). GLO1 up regulation was strongly linked to early biochemical recurrence in univariate analysis (P < 0.0001) and predicted poor prognosis independent from most (except from nodal stage) established prognostic parameters in multivariate analysis (P ≤ 0.03).CONCLUSIONS: GLO1 upregulation is linked to aggressive prostate cancers characterized by ERG fusion and PTEN deletion. The strong and independent prognostic value makes it a promising candidate for routine diagnostic applications either alone or in combination with other markers.
KW - Aged
KW - Biomarkers, Tumor
KW - Humans
KW - Immunohistochemistry
KW - Kallikreins
KW - Lactoylglutathione Lyase
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local
KW - Prognosis
KW - Prostate-Specific Antigen
KW - Prostatic Neoplasms
KW - Tissue Array Analysis
KW - Journal Article
U2 - 10.1002/pros.23431
DO - 10.1002/pros.23431
M3 - SCORING: Journal article
C2 - 28929505
VL - 77
SP - 1528
EP - 1538
JO - PROSTATE
JF - PROSTATE
SN - 0270-4137
IS - 15
ER -
