Deletion of 8p is an independent prognostic parameter in prostate cancer
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Deletion of 8p is an independent prognostic parameter in prostate cancer. / Kluth, Martina; Amschler, Nina Nadine; Galal, Rami; Möller-Koop, Christina; Barrow, Phillipp; Tsourlakis, Maria Christina; Jacobsen, Frank; Hinsch, Andrea; Wittmer, Corinna; Steurer, Stefan; Krech, Till; Büscheck, Franziska; Clauditz, Till Sebastian; Beyer, Burkhard; Wilczak, Waldemar; Graefen, Markus; Huland, Hartwig; Minner, Sarah; Schlomm, Thorsten; Sauter, Guido; Simon, Ronald.
in: ONCOTARGET, Jahrgang 8, Nr. 1, 03.01.2017, S. 379-392.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Deletion of 8p is an independent prognostic parameter in prostate cancer
AU - Kluth, Martina
AU - Amschler, Nina Nadine
AU - Galal, Rami
AU - Möller-Koop, Christina
AU - Barrow, Phillipp
AU - Tsourlakis, Maria Christina
AU - Jacobsen, Frank
AU - Hinsch, Andrea
AU - Wittmer, Corinna
AU - Steurer, Stefan
AU - Krech, Till
AU - Büscheck, Franziska
AU - Clauditz, Till Sebastian
AU - Beyer, Burkhard
AU - Wilczak, Waldemar
AU - Graefen, Markus
AU - Huland, Hartwig
AU - Minner, Sarah
AU - Schlomm, Thorsten
AU - Sauter, Guido
AU - Simon, Ronald
PY - 2017/1/3
Y1 - 2017/1/3
N2 - Deletion of chromosome 8p is the second most frequent genomic alteration in prostate cancer. To better understand its clinical significance, 8p deletion was analyzed by fluorescence in-situ hybridization on a prostate cancer tissue microarray. 8p deletion was found in 2,581 of 7,017 cancers (36.8%), and was linked to unfavorable tumor phenotype. 8p deletion increased from 29.5% in 4,456 pT2 and 47.8% in 1,598 pT3a to 53.0% in 931 pT3b-pT4 cancers (P < 0,0001). Deletions of 8p were detected in 25.5% of 1,653 Gleason ≤ 3 + 3, 36.6% of 3,880 Gleason 3 + 4, 50.2% of 1,090 Gleason 4 + 3, and 51.1% of 354 Gleason ≥ 4 + 4 tumors (P < 0,0001). 8p deletions were strongly linked to biochemical recurrence (P < 0.0001) independently from established pre- and postoperative prognostic factors (P = 0.0100). However, analysis of morphologically defined subgroups revealed, that 8p deletion lacked prognostic significance in subgroups with very good (Gleason ≤ 3 + 3, 3 + 4 with ≤ 5% Gleason 4) or very poor prognosis (pT3b, Gleason ≥ 8, pN1). 8p deletions were markedly more frequent in cancers with (53.5%) than without PTEN deletions (36.4%; P < 0,0001) and were slightly more frequent in ERG-positive (40.9%) than in ERG-negative cancers (34.7%, P < 0.0001) due to the association with the ERG-associated PTEN deletion. Cancers with 8p/PTEN co-deletions had a strikingly worse prognosis than cancers with deletion of PTEN or 8p alone (P ≤ 0.0003). In summary, 8p deletion is an independent prognostic parameter in prostate cancer that may act synergistically with PTEN deletions. Even statistically independent prognostic biomarkers like 8p may have limited clinical impact in morphologically well defined high or low risk cancers.
AB - Deletion of chromosome 8p is the second most frequent genomic alteration in prostate cancer. To better understand its clinical significance, 8p deletion was analyzed by fluorescence in-situ hybridization on a prostate cancer tissue microarray. 8p deletion was found in 2,581 of 7,017 cancers (36.8%), and was linked to unfavorable tumor phenotype. 8p deletion increased from 29.5% in 4,456 pT2 and 47.8% in 1,598 pT3a to 53.0% in 931 pT3b-pT4 cancers (P < 0,0001). Deletions of 8p were detected in 25.5% of 1,653 Gleason ≤ 3 + 3, 36.6% of 3,880 Gleason 3 + 4, 50.2% of 1,090 Gleason 4 + 3, and 51.1% of 354 Gleason ≥ 4 + 4 tumors (P < 0,0001). 8p deletions were strongly linked to biochemical recurrence (P < 0.0001) independently from established pre- and postoperative prognostic factors (P = 0.0100). However, analysis of morphologically defined subgroups revealed, that 8p deletion lacked prognostic significance in subgroups with very good (Gleason ≤ 3 + 3, 3 + 4 with ≤ 5% Gleason 4) or very poor prognosis (pT3b, Gleason ≥ 8, pN1). 8p deletions were markedly more frequent in cancers with (53.5%) than without PTEN deletions (36.4%; P < 0,0001) and were slightly more frequent in ERG-positive (40.9%) than in ERG-negative cancers (34.7%, P < 0.0001) due to the association with the ERG-associated PTEN deletion. Cancers with 8p/PTEN co-deletions had a strikingly worse prognosis than cancers with deletion of PTEN or 8p alone (P ≤ 0.0003). In summary, 8p deletion is an independent prognostic parameter in prostate cancer that may act synergistically with PTEN deletions. Even statistically independent prognostic biomarkers like 8p may have limited clinical impact in morphologically well defined high or low risk cancers.
U2 - 10.18632/oncotarget.13425
DO - 10.18632/oncotarget.13425
M3 - SCORING: Journal article
C2 - 27880722
VL - 8
SP - 379
EP - 392
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 1
ER -