Nuclear localization of factor inhibitor hypoxia-inducible factor in prostate cancer is associated with poor prognosis

Nadeem Shaida, Peter Chan, Helen Turley, Catherine M. Jones, Suresh Kanga, Robert W. Ritchie, Peter R. Malone, Adrian L. Harris, Stephen B. Fox

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9 Citations (Scopus)

Abstract

Purpose: We determined the role of factor inhibiting hypoxia-inducible factor-1 in prostate cancer specimens. Materials and 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.

Original languageEnglish
Pages (from-to)1513-1518
Number of pages6
JournalJournal of Urology
Volume185
Issue number4
DOIs
Publication statusPublished - 1 Apr 2011
Externally publishedYes

Keywords

  • HIF1AN protein
  • human
  • hypoxia-inducible factor 1
  • local
  • neoplasm recurrence
  • prostate
  • prostatic neoplasms

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