title: The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy.
abstract: OBJECTIVE
  Androgens stimulate the production of hypoxia-inducible factor (HIF1α) and ultimately vascular endothelial growth factor (VEGF-A). Additionally, epithelial growth factor (EGF) mediates HIF1α production. Carbonic anhydrase IX (CAIX) expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT).
  
  
  METHODS
  Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2), with prostate cancer (mean PSA, 13.3 ± 3.7), were treated with radiation therapy (RT, median dose, 74 Gy). Fifty seven (55.3%) patients received ADT (median duration, 6 months; range, 0 - 24). Median follow-up was 97.6 months (range, 5.9 - 206.8).
  
  
  RESULTS
  Higher EGFR expression was significantly (p = 0.04) correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (p = 0.02) prognostic factor for biological progression-free survival (bPFS). A trend towards significance (p = 0.05) was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (p = 0.01) and high EGFR (p = 0.04) expression remained significant adverse prognostic factors.
  
  
  CONCLUSIONS
  Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis.
authors.affiliation: Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland. damien.weber@hcuge.ch
authors.forename: Damien C
authors.initials: DC
authors.lastname: Weber
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Tille
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Egger
authors.forename: Mahomet
authors.initials: M
authors.lastname: Laouiti
authors.forename: Karim
authors.initials: K
authors.lastname: Hammad
authors.forename: Perrine
authors.initials: P
authors.lastname: Granger
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: Raymond
authors.initials: R
authors.lastname: Miralbell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D011878:Radiotherapy; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors