title: Chromatin changes predict recurrence after radical prostatectomy.
abstract: BACKGROUND
  Pathological evaluations give the best prognostic markers for prostate cancer patients after radical prostatectomy, but the observer variance is substantial. These risk assessments should be supported and supplemented by objective methods for identifying patients at increased risk of recurrence. Markers of epigenetic aberrations have shown promising results in several cancer types and can be assessed by automatic analysis of chromatin organisation in tumour cell nuclei.
  
  
  METHODS
  A consecutive series of 317 prostate cancer patients treated with radical prostatectomy at a national hospital between 1987 and 2005 were followed for a median of 10 years (interquartile range, 7-14). On average three tumour block samples from each patient were included to account for tumour heterogeneity. We developed a novel marker, termed Nucleotyping, based on automatic assessment of disordered chromatin organisation, and validated its ability to predict recurrence after radical prostatectomy.
  
  
  RESULTS
  Nucleotyping predicted recurrence with a hazard ratio (HR) of 3.3 (95% confidence interval (CI), 2.1-5.1). With adjustment for clinical and pathological characteristics, the HR was 2.5 (95% CI, 1.5-4.1). An updated stratification into three risk groups significantly improved the concordance with patient outcome compared with a state-of-the-art risk-stratification tool (P<0.001). The prognostic impact was most evident for the patients who were high-risk by clinical and pathological characteristics and for patients with Gleason score 7.
  
  
  CONCLUSIONS
  A novel assessment of epigenetic aberrations was capable of improving risk stratification after radical prostatectomy.
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Department of Informatics, University of Oslo, Oslo NO-0316, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Tarjei S
authors.initials: TS
authors.lastname: Hveem
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Department of Informatics, University of Oslo, Oslo NO-0316, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kleppe
authors.affiliation: Department of Pathology, Oslo University Hospital, Oslo NO-0424, Norway.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Vlatkovic
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Ersvær
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Håkon
authors.initials: H
authors.lastname: Wæhre
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Nielsen
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Marte Avranden
authors.initials: MA
authors.lastname: Kjær
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Manohar
authors.initials: M
authors.lastname: Pradhan
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Rolf Anders
authors.initials: RA
authors.lastname: Syvertsen
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: John Arne
authors.initials: JA
authors.lastname: Nesheim
authors.affiliation: Department of Informatics, University of Oslo, Oslo NO-0316, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Department of Informatics, University of Oslo, Oslo NO-0316, Norway.
authors.forename: Fritz
authors.initials: F
authors.lastname: Albregtsen
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.|Department of Informatics, University of Oslo, Oslo NO-0316, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo NO-0424, Norway.|Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Håvard E
authors.initials: HE
authors.lastname: Danielsen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000601:surgery / Q000648:ultrastructure*; D000368:Aged; D000782:Aneuploidy; D002467:Cell Nucleus / Q000648:ultrastructure; D002843:Chromatin / Q000648:ultrastructure*; D044127:Epigenesis, Genetic; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000235:genetics; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000601:surgery / Q000648:ultrastructure*; D018570:Risk Assessment; D012720:Severity of Illness Index; D017211:Treatment Failure
chemical_list: D002843:Chromatin