title: Genomic deletion of chromosome 12p is an independent prognostic marker in prostate cancer.
abstract: 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.
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Martina
authors: M
authors: Kluth
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Ramin
authors: R
authors: Ahrary
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Claudia
authors: C
authors: Hube-Magg
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Malik
authors: M
authors: Ahmed
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Heinke
authors: H
authors: Volta
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Catina
authors: C
authors: Schwemin
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Stefan
authors: S
authors: Steurer
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Corinna
authors: C
authors: Wittmer
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Waldemar
authors: W
authors: Wilczak
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Eike
authors: E
authors: Burandt
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Till
authors: T
authors: Krech
authors: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors: Meike
authors: M
authors: Adam
authors: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors: Uwe
authors: U
authors: Michl
authors: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors: Hans
authors: H
authors: Heinzer
authors: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors: Georg
authors: G
authors: Salomon
authors: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors: Markus
authors: M
authors: Graefen
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Christina
authors: C
authors: Koop
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Sarah
authors: S
authors: Minner
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Ronald
authors: R
authors: Simon
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Guido
authors: G
authors: Sauter
authors: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.|Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Germany.
authors: Thorsten
authors: T
authors: Schlomm
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: 12p deletion; CDKN1B; p27; prognostic marker; prostate cancer