title: Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer.
abstract: BACKGROUND
  The natural history of prostate cancer is highly variable and difficult to predict. We report on the prognostic value of phosphatase and tensin homologue (PTEN) loss in a cohort of 675 men with conservatively managed prostate cancer diagnosed by transurethral resection of the prostate.
  
  
  METHODS
  The PTEN status was assayed by immunohistochemistry (PTEN IHC) and fluorescent in situ hybridisation (PTEN FISH). The primary end point was death from prostate cancer.
  
  
  RESULTS
  The PTEN IHC loss was observed in 18% cases. This was significantly associated with prostate cancer death in univariate analysis (hazard ratio (HR)=3.51; 95% CI 2.60-4.73; P=3.1 × 10(-14)). It was highly predictive of prostate cancer death in the 50% of patients with a low risk score based on Gleason score, PSA, Ki-67 and extent of disease (HR=7.4; 95% CI 2.2-24.6; P=0.012) ), but had no prognostic value in the higher risk patients. The PTEN FISH loss was only weakly associated with PTEN IHC loss (κ=0.5). Both PTEN FISH loss and amplification were univariately predictive of death from prostate cancer, but this was not maintained in the multivariate analyses.
  
  
  CONCLUSIONS
  In low-risk patients, PTEN IHC loss adds prognostic value to Gleason score, PSA, Ki-67 and extent of disease.
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, EC1M 6BQ, UK. j.cuzick@qmul.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Cuzick
authors.forename: Z H
authors.initials: ZH
authors.lastname: Yang
authors.forename: G
authors.initials: G
authors.lastname: Fisher
authors.forename: E
authors.initials: E
authors.lastname: Tikishvili
authors.forename: S
authors.initials: S
authors.lastname: Stone
authors.forename: J S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: N
authors.initials: N
authors.lastname: Camacho
authors.forename: S
authors.initials: S
authors.lastname: Merson
authors.forename: D
authors.initials: D
authors.lastname: Brewer
authors.forename: C S
authors.initials: CS
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
authors.forename: H
authors.initials: H
authors.lastname: Møller
authors.forename: P
authors.initials: P
authors.lastname: Scardino
authors.forename: Z
authors.initials: Z
authors.lastname: Sangale
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000601:surgery; D020728:Transurethral Resection of Prostate
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017430:Prostate-Specific Antigen