High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer
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High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer. / Melling, Nathaniel; Rashed, Masoud; Schroeder, Cornelia; Hube-Magg, Claudia; Kluth, Martina; Lang, Dagmar; Simon, Ronald; Möller-Koop, Christina; Steurer, Stefan; Sauter, Guido; Jacobsen, Frank; Büscheck, Franziska; Wittmer, Corinna; Clauditz, Till; Krech, Till; Tsourlakis, Maria Christina; Minner, Sarah; Huland, Hartwig; Graefen, Markus; Budäus, Lars; Thederan, Imke; Salomon, Georg; Schlomm, Thorsten; Wilczak, Waldemar.
in: INT J MOL SCI, Jahrgang 18, Nr. 2, 29.01.2017, S. 286.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer
AU - Melling, Nathaniel
AU - Rashed, Masoud
AU - Schroeder, Cornelia
AU - Hube-Magg, Claudia
AU - Kluth, Martina
AU - Lang, Dagmar
AU - Simon, Ronald
AU - Möller-Koop, Christina
AU - Steurer, Stefan
AU - Sauter, Guido
AU - Jacobsen, Frank
AU - Büscheck, Franziska
AU - Wittmer, Corinna
AU - Clauditz, Till
AU - Krech, Till
AU - Tsourlakis, Maria Christina
AU - Minner, Sarah
AU - Huland, Hartwig
AU - Graefen, Markus
AU - Budäus, Lars
AU - Thederan, Imke
AU - Salomon, Georg
AU - Schlomm, Thorsten
AU - Wilczak, Waldemar
PY - 2017/1/29
Y1 - 2017/1/29
N2 - γ-glutamyl-hydrolase (GGH) is a ubiquitously-expressed enzyme that regulates intracellular folate metabolism for cell proliferation, DNA synthesis, and repair. Employing GGH immunohistochemistry on a tissue microarray with 12,427 prostate cancers, we found that GGH expression was negative to low in normal prostate epithelium, whereas 88.3% of our 10,562 interpretable cancers showed GGH expression. GGH staining was considered as low intensity in 49.6% and as high intensity in 38.6% of cancers. High GGH expression was linked to the TMPRSS2:ERG-fusion positive subset of cancers (p < 0.0001), advanced pathological tumor stage, and high Gleason grade (p < 0.0001 each). Further analysis revealed that these associations were merely driven by the subset of ERG-negative cancers, High GGH expression was weakly linked to early biochemical recurrence in ERG negative cancers (p < 0.0001) and independent from established histo-pathological parameters. Moreover, GGH expression was linked to features of genetic instability, including presence of recurrent deletions at 3p, 5q, 6q, and 10q (PTEN, p ≤ 0.01 each), as well as to accelerated cell proliferation as measured by Ki67 immunohistochemistry (p < 0.0001). In conclusion, the results of our study identify GGH as an ERG subtype specific molecular marker with modest prognostic relevance, which may have clinical relevance if analyzed in combination with other molecular markers.
AB - γ-glutamyl-hydrolase (GGH) is a ubiquitously-expressed enzyme that regulates intracellular folate metabolism for cell proliferation, DNA synthesis, and repair. Employing GGH immunohistochemistry on a tissue microarray with 12,427 prostate cancers, we found that GGH expression was negative to low in normal prostate epithelium, whereas 88.3% of our 10,562 interpretable cancers showed GGH expression. GGH staining was considered as low intensity in 49.6% and as high intensity in 38.6% of cancers. High GGH expression was linked to the TMPRSS2:ERG-fusion positive subset of cancers (p < 0.0001), advanced pathological tumor stage, and high Gleason grade (p < 0.0001 each). Further analysis revealed that these associations were merely driven by the subset of ERG-negative cancers, High GGH expression was weakly linked to early biochemical recurrence in ERG negative cancers (p < 0.0001) and independent from established histo-pathological parameters. Moreover, GGH expression was linked to features of genetic instability, including presence of recurrent deletions at 3p, 5q, 6q, and 10q (PTEN, p ≤ 0.01 each), as well as to accelerated cell proliferation as measured by Ki67 immunohistochemistry (p < 0.0001). In conclusion, the results of our study identify GGH as an ERG subtype specific molecular marker with modest prognostic relevance, which may have clinical relevance if analyzed in combination with other molecular markers.
U2 - 10.3390/ijms18020286
DO - 10.3390/ijms18020286
M3 - SCORING: Journal article
C2 - 28146062
VL - 18
SP - 286
JO - INT J MOL SCI
JF - INT J MOL SCI
SN - 1661-6596
IS - 2
ER -