title: Deletion of 8p is an independent prognostic parameter in prostate cancer.
abstract: 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.
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kluth
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Nina Nadine
authors.initials: NN
authors.lastname: Amschler
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Rami
authors.initials: R
authors.lastname: Galal
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Möller-Koop
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Phillipp
authors.initials: P
authors.lastname: Barrow
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jacobsen
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hinsch
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wittmer
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Büscheck
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Till Sebastian
authors.initials: TS
authors.lastname: Clauditz
authors.affiliation: Martini-Clinic, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Beyer
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.affiliation: Martini-Clinic, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Martini-Clinic, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Martini-Clinic, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.|Department of Urology, Section for Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute of Pathology, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8; D018450:Disease Progression; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D046888:Tissue Array Analysis / Q000379:methods; D000071230:Transcriptional Regulator ERG / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: NKX3.1; PTEN; TMPRSS2:ERG; prostate cancer; tissue microarray