Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of PTEN deleted prostate cancers
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Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of PTEN deleted prostate cancers. / Luebke, Andreas M; Attarchi-Tehrani, Ali; Meiners, Jan; Hube-Magg, Claudia; Lang, Dagmar S; Kluth, Martina; Tsourlakis, Maria Christina; Minner, Sarah; Simon, Ronald; Sauter, Guido; Büscheck, Franziska; Jacobsen, Frank; Hinsch, Andrea; Steurer, Stefan; Schlomm, Thorsten; Huland, Hartwig; Graefen, Markus; Haese, Alexander; Heinzer, Hans; Clauditz, Till S; Burandt, Eike; Wilczak, Waldemar; Höflmayer, Doris.
in: CANCER BIOL MED, Jahrgang 16, Nr. 2, 05.2019, S. 319-330.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of PTEN deleted prostate cancers
AU - Luebke, Andreas M
AU - Attarchi-Tehrani, Ali
AU - Meiners, Jan
AU - Hube-Magg, Claudia
AU - Lang, Dagmar S
AU - Kluth, Martina
AU - Tsourlakis, Maria Christina
AU - Minner, Sarah
AU - Simon, Ronald
AU - Sauter, Guido
AU - Büscheck, Franziska
AU - Jacobsen, Frank
AU - Hinsch, Andrea
AU - Steurer, Stefan
AU - Schlomm, Thorsten
AU - Huland, Hartwig
AU - Graefen, Markus
AU - Haese, Alexander
AU - Heinzer, Hans
AU - Clauditz, Till S
AU - Burandt, Eike
AU - Wilczak, Waldemar
AU - Höflmayer, Doris
PY - 2019/5
Y1 - 2019/5
N2 - Objective: Prostate secretory protein of 94 amino acids (PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer; however, its prognostic value is disputed.Methods: Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was studied.Results: PSP94 expression was increased in benign prostatic hyperplasia; however, it was downregulated in 48% and negative in 42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression (P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis ( P <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52% in pT3b-pT4 ( P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8 ( P < 0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect ( P < 0.0001). However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10% (P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.Conclusions: The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.
AB - Objective: Prostate secretory protein of 94 amino acids (PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer; however, its prognostic value is disputed.Methods: Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was studied.Results: PSP94 expression was increased in benign prostatic hyperplasia; however, it was downregulated in 48% and negative in 42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression (P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis ( P <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52% in pT3b-pT4 ( P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8 ( P < 0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect ( P < 0.0001). However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10% (P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.Conclusions: The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.
U2 - 10.20892/j.issn.2095-3941.2018.0384
DO - 10.20892/j.issn.2095-3941.2018.0384
M3 - SCORING: Journal article
C2 - 31516752
VL - 16
SP - 319
EP - 330
JO - CANCER BIOL MED
JF - CANCER BIOL MED
SN - 2095-3941
IS - 2
ER -