Genomic deletion of chromosome 12p is an independent prognostic marker in prostate cancer
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Martina Kluth1, Ramin Ahrary1, Claudia Hube-Magg1, Malik Ahmed1, Heinke Volta1, Catina Schwemin1, Stefan Steurer1, Corinna Wittmer1, Waldemar Wilczak1, Eike Burandt1, Till Krech1, Meike Adam2, Uwe Michl2, Hans Heinzer2, Georg Salomon2, Markus Graefen2, Christina Koop1, Sarah Minner1, Ronald Simon1, Guido Sauter1, Thorsten Schlomm2,3
1Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany
2Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany
3Dept. of Urology, Section for translational prostate cancer research, University Medical Center Hamburg-Eppendorf, Germany
Ronald Simon, e-mail: firstname.lastname@example.org
Keywords: 12p deletion, prostate cancer, CDKN1B, p27, prognostic marker
Received: May 27, 2015 Accepted: July 03, 2015 Published: July 21, 2015
Deletion of 12p is a recurrent alteration in prostate cancer, but the prevalence and clinical consequences of this alteration have not been studied in detail. Dual labeling fluorescence in situ hybridization using probes for 12p13 (CDKN1B; p27) and centromere 12 as a reference was used to successfully analyze more than 3700 prostate cancers with clinical follow-up data assembled in a tissue microarray format. CDKN1B was selected as a probe because it is located in the center of the deletion, which spans > 10 Mb and includes > 50 genes in 80% of cancers with 12p deletion. Deletion of 12p was found in 13.7% of cancers and included 13.5% heterozygous and 0.2% homozygous deletions. 12p deletion were linked to advanced tumor stage (p < 0.0001), high Gleason grade (p < 0.0001), rapid tumor cell proliferation (p < 0.0001), lymph node metastasis (p = 0.0004), and biochemical recurrence (p = 0.0027). Multivariate analysis including pT stage (p < 0.0001), Gleason grade (p < 0.0001), pN status (p = 0.0001), preoperative PSA levels (p = 0.0001), and resection margin status (p = 0.0001) revealed an independent prognostic value of 12p deletion (p = 0.0014). Deletion of 12p was unrelated to the ERG fusion status. Deletion of 12p was only marginally linked to reduced p27 expression, which by itself was unrelated to clinical outcome. This argues against p27 as the key target gene of 12p deletions. In summary, the results of our study demonstrate that 12p deletion is frequent in prostate cancer and provides independent prognostic information. 12p deletion analysis alone, or in combination with other prognostic parameters may thus have clinical utility.
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