title: Nuclear localization of factor inhibitor hypoxia-inducible factor in prostate cancer is associated with poor prognosis.
abstract: OBJECTIVE
  We determined the role of factor inhibiting hypoxia-inducible factor-1 in prostate cancer specimens.
  
  
  METHODS
  A tissue microarray of 152 prostate cancers was constructed and stained for factor inhibiting hypoxia-inducible factor-1, hypoxia-inducible factor-1α and 2α, and glucose transporter 1 as a prototypical downstream target of hypoxia-inducible factor-1α. Correlation analysis was done between these variables, and between factor inhibiting hypoxia-inducible factor-1, and clinical and pathological variables, including prostate specific antigen as a surrogate of recurrence.
  
  
  RESULTS
  Factor inhibiting hypoxia-inducible factor-1 was expressed in the cytoplasm and/or the nucleus in 86.5% of tumors, including exclusive cytoplasmic expression in 51.3% and exclusive nuclear expression in 5.3%. Any nuclear and exclusive expression of factor inhibiting hypoxia-inducible factor was associated with poor prognosis on univariate analysis (p = 0.007 and 0.042, respectively). On multivariate analysis men with nuclear expression in tumors were twice as likely to experience recurrence (p = 0.034).
  
  
  CONCLUSIONS
  Factor inhibiting hypoxia-inducible factor-1 is widely expressed in prostate tumors. Its differential subcellular expression suggests that regulation of its expression is an important factor in the activity of the hypoxia-inducible factor pathway. Its modulation may help treat hypoxia-inducible factor driven aggressive prostate cancer.
authors.affiliation: Harold Hopkins Department of Urology, Royal Berkshire Hospital, Oxford, United Kingdom.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Shaida
authors.forename: Peter
authors.initials: P
authors.lastname: Chan
authors.forename: Helen
authors.initials: H
authors.lastname: Turley
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Jones
authors.forename: Suresh
authors.initials: S
authors.lastname: Kanga
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ritchie
authors.forename: Peter R
authors.initials: PR
authors.lastname: Malone
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
mesh_terms: D002467:Cell Nucleus / Q000737:chemistry; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology; D012097:Repressor Proteins / Q000032:analysis / Q000502:physiology*; D015996:Survival Rate
chemical_list: D012097:Repressor Proteins; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human