title: Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence.
abstract: Multiple biomarkers are needed to distinguish aggressive from indolent prostate cancer. We tested the prognostic utility of a three-marker fluorescent in situ hybridization (FISH) panel (TMPRSS2/ERG rearrangements, AR gain, and PTEN deletion) in a retrospective cohort (n = 210; median follow-up, 5.7 years). PTEN deletion was associated with an increased risk of biochemical recurrence (BcR; hazard ratio, 3.58; 95% CI, 1.39-9.22; P < 0.01) by multivariable Cox regression analyses and earlier BcR (P < 0.02) by Kaplan-Meier analysis. AR gain coexisted with X-chromosome gain and was associated with advanced tumor stage. When this panel was applied, two categories of combinatorial abnormalities proved clinically important. First, PTEN deletion without TMPRSS2/ERG rearrangement was enriched in pT3/4 tumors (70% versus 48%) and tumors with Gleason grades of 8 to 9 (60% versus 17%) compared with the entire cohort. These patients had earlier BcR than patients with normal FISH panel results (P < 0.01). In contrast, patients with PTEN deletion and ERG rearrangement had a BcR rate similar to patients who tested normal for all three markers (P > 0.1). Second, AR gain and concurrent trisomy 10 without TMPRSS2/ERG rearrangement were enriched in pT3/4 tumors and tumors with Gleason grades of 8 to 9. The three-marker FISH panel demonstrated prognostic utility and identified genomic aberrations associated with advanced disease state and early BcR in prostate cancer.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Urology, University of Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Claudio
authors.initials: C
authors.lastname: Jeldres
authors.affiliation: Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Lena
authors.initials: L
authors.lastname: Glaskova
authors.affiliation: Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Friedman
authors.affiliation: Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schroeder
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
authors.affiliation: Department of Urology, Virginia Mason Medical Center, Seattle, Washington. Electronic address: christopher.porter@vmmc.org.
authors.forename: Christopher
authors.initials: C
authors.lastname: Porter
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington. Electronic address: mfang@fhcrc.org.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002869:Chromosome Aberrations; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011379:Prognosis; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human