title: Prognostic value of survivin in locally advanced prostate cancer: study based on RTOG 8610.
abstract: OBJECTIVE
  To examine the prognostic value of nuclear and cytoplasmic survivin expression in men with locally advanced prostate cancer who were enrolled in Radiation Therapy Oncology Group (RTOG) protocol 8610.
  
  
  METHODS
  RTOG 8610 was a Phase III randomized study comparing the effect of radiotherapy plus short-term androgen deprivation with radiotherapy alone. Of the 456 eligible patients, 68 patients had suitably stained tumor material for nuclear survivin analysis and 65 patients for cytoplasmic survivin.
  
  
  RESULTS
  Compared with patients with nuclear survivin intensity scores of <or=191.2, those with intensity scores >191.2 had significantly improved prostate cancer survival (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.20-1.00, p = 0.0452). On multivariate analysis, nuclear survivin intensity scores >191.2 were significantly associated with improved overall survival (HR, 0.46; 95% CI, 0.25-0.86; p = 0.0156) and prostate cancer survival (HR, 0.36; 95% CI, 0.16-0.84; p = 0.0173). On univariate analysis, compared with patients with cytoplasmic survivin integrated optical density <or=82.7, those with an integrated optical density >82.7 showed a significantly increased risk of local progression (HR, 2.49; 95% CI, 1.03-6.01; p = 0.0421).
  
  
  CONCLUSIONS
  Nuclear overexpression of survivin was associated with improved overall and prostate cancer survival on multivariate analysis, and cytoplasmic overexpression of survivin was associated with increased rate of local progression on univariate analysis in patients with locally advanced prostate cancer treated on RTOG 8610. Our results might reflect the different functions of survivin and its splice variants, which are known to exist in distinct subcellular compartments.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Alex
authors.initials: A
authors.lastname: Ho
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Hammond
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: R Scott
authors.initials: RS
authors.lastname: Bermudez
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Pilepich
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.forename: Howard
authors.initials: H
authors.lastname: Sandler
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Khor
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D002467:Cell Nucleus / Q000737:chemistry; D017326:Clinical Trials, Phase III as Topic; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D000077022:Survivin
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin