The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer
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The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer. / Lennartz, Maximilian; Minner, Sarah; Brasch, Sophie ; Wittmann, Hilko ; Paterna, Leonard ; Angermeier, Katja; Öztürk, Eray ; Shihada, Rami ; Ruge, Mingu ; Kluth, Martina; Koop, Christina; Wilczak, Waldemar; Krech, Till; Lebok, Patrick; Wittmer, Corinna; Heinzer, Hans; Steuber, Thomas; Adam, Meike; Huland, Hartwig; Graefen, Markus; Haese, Alexander; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten.
in: CLIN CANCER RES, Jahrgang 22, Nr. 11, 01.06.2016, S. 2802-11.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer
AU - Lennartz, Maximilian
AU - Minner, Sarah
AU - Brasch, Sophie
AU - Wittmann, Hilko
AU - Paterna, Leonard
AU - Angermeier, Katja
AU - Öztürk, Eray
AU - Shihada, Rami
AU - Ruge, Mingu
AU - Kluth, Martina
AU - Koop, Christina
AU - Wilczak, Waldemar
AU - Krech, Till
AU - Lebok, Patrick
AU - Wittmer, Corinna
AU - Heinzer, Hans
AU - Steuber, Thomas
AU - Adam, Meike
AU - Huland, Hartwig
AU - Graefen, Markus
AU - Haese, Alexander
AU - Simon, Ronald
AU - Sauter, Guido
AU - Schlomm, Thorsten
N1 - ©2016 American Association for Cancer Research.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - PURPOSE: Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer.EXPERIMENTAL DESIGN: We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers.RESULT: The DNA status was diploid in 67.8%, tetraploid in 25.6%, and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (P < 0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (P < 0.0001 each). However, 40% of patients with Gleason score ≥4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason ≥4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (P < 0.0001), tetraploid (P < 0.0001), and aneuploid cancers (P = 0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the "combined DNA status" as a strong independent predictor of poor patient outcome.CONCLUSIONS: The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer. Clin Cancer Res; 22(11); 2802-11. ©2016 AACR.
AB - PURPOSE: Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer.EXPERIMENTAL DESIGN: We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers.RESULT: The DNA status was diploid in 67.8%, tetraploid in 25.6%, and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (P < 0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (P < 0.0001 each). However, 40% of patients with Gleason score ≥4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason ≥4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (P < 0.0001), tetraploid (P < 0.0001), and aneuploid cancers (P = 0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the "combined DNA status" as a strong independent predictor of poor patient outcome.CONCLUSIONS: The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer. Clin Cancer Res; 22(11); 2802-11. ©2016 AACR.
KW - Journal Article
U2 - 10.1158/1078-0432.CCR-15-0635
DO - 10.1158/1078-0432.CCR-15-0635
M3 - SCORING: Journal article
C2 - 26813356
VL - 22
SP - 2802
EP - 2811
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 11
ER -