title: The value of EZH2, p27(kip1), BMI-1 and MIB-1 on biopsy specimens with low-risk prostate cancer in selecting men with significant prostate cancer at prostatectomy.
abstract: OBJECTIVE
  To assess the additional prognostic value of the molecular markers EZH2, MIB-1, p27(kip1) and BMI-1 on needle biopsies from men with low-risk prostate cancer, as this disease in needle biopsies shows a heterogeneous clinical outcome, and while it is known that the expression of these tissue markers is predictive of the clinical outcome after radical prostatectomy (RP) their value in prostate biopsies is largely unknown.
  
  
  METHODS
  The study included men participating in a screening study, diagnosed with low-risk prostate cancer and subsequently treated with RP. Immunohistochemical staining for EZH2, MIB-1, p27(kip1) and BMI-1 on the needle biopsies were (semi)quantitatively scored and expression levels were related to significant disease at RP. Clinical low-risk prostate cancer was defined as a prostate-specific antigen (PSA) level of < or =10 ng/mL, clinical T-stage < or =2, biopsy Gleason score < or =6, a PSA density of <0.20 ng/mL/g and two or fewer positive cores. Significant PC at RP was defined as presence of any of extracapsular extension, Gleason pattern 4/5, or tumour volume > or =0.5 mL.
  
  
  RESULTS
  In all, 86 biopsy specimens were included; there was high EZH2 expression (>1.0%) in 42% and a low p27(kip) expression (<90%) in 63%. Significant disease was present in 44 (51%) RP specimens. A high EZH2 (odds ratio 3.19, P = 0.043) and a low p27(kip1) (4.69, P = 0.036) were independent predictors for significant prostate cancer at RP.
  
  
  CONCLUSIONS
  The determination of EZH2 and p27(kip1) on diagnostic needle biopsies supports the selection of men with indolent prostate cancer at RP. Especially p27(kip1) could improve the pretreatment risk assessment of patients with low-risk prostate cancer.
authors.affiliation: Department of Urology, Erasmus Medical Center, Rotterdam, the Netherlands. t.wolters@erasmusmc.nl
authors.forename: Tineke
authors.initials: T
authors.lastname: Wolters
authors.forename: Kees J
authors.initials: KJ
authors.lastname: Vissers
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Schröder
authors.forename: Geert J L H
authors.initials: GJ
authors.lastname: van Leenders
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000032:analysis*; D000071221:Enhancer of Zeste Homolog 2 Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D017430:Prostate-Specific Antigen; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D012097:Repressor Proteins / Q000032:analysis*; D018570:Risk Assessment; D012307:Risk Factors; D014157:Transcription Factors / Q000032:analysis*; D044767:Ubiquitin-Protein Ligases / Q000032:analysis*
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; C436291:CDKN1B protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; C513496:MIB1 ligase, human; D063150:Polycomb Repressive Complex 1; D044767:Ubiquitin-Protein Ligases; D017430:Prostate-Specific Antigen