title: Relative 8q gain predicts disease-specific survival irrespective of the TMPRSS2-ERG fusion status in diagnostic biopsies of prostate cancer.
abstract: Screening tools have greatly improved prostate cancer (PCa) detection, but the disease course is heterogeneous, and standard clinicopathological parameters do not fully discriminate aggressive from indolent tumors. To evaluate the prognostic value of the TMPRSS2-ERG fusion gene combined with chromosome arm 8q relative gain in diagnostic biopsies of PCa, we studied a consecutive series of 200 diagnostic needle biopsies from patients with 10-year disease-specific survival data. TMPRSS2-ERG fusion gene status and relative 8q gain were assessed by fluorescent in situ hybridization in whole formalin fixed paraffin-embedded biopsies. The TMPRSS2-ERG fusion gene was detected in 43.5% of PCa and was associated with lower Gleason score (P = 0.045), whereas relative 8q gain was present in 48% of PCa and was associated in high-Gleason score (P < 0.001). ERG rearrangement alone was not associated with clinical outcome, whereas relative 8q gain predicted worse disease-specific survival in PCa patients both with and without the TMPRSS2-ERG fusion gene (P < 0.001), independently of Gleason score, clinical stage, and treatment modality. We conclude that relative 8q gain in diagnostic needle biopsies is a poor prognostic factor independent of the TMPRSS2-ERG fusion gene status and of standard clinicopathological parameters.
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
authors.forename: João D
authors.initials: JD
authors.lastname: Barros-Silva
authors.forename: Franclim R
authors.initials: FR
authors.lastname: Ribeiro
authors.forename: Angelo
authors.initials: A
authors.lastname: Rodrigues
authors.forename: Ricardo
authors.initials: R
authors.lastname: Cruz
authors.forename: Ana T
authors.initials: AT
authors.lastname: Martins
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
mesh_terms: D000368:Aged; D001706:Biopsy / Q000379:methods; D002898:Chromosomes, Human, Pair 8; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D053208:Kaplan-Meier Estimate; D008297:Male; D015514:Oncogene Proteins, Fusion; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human