title: Expression of hypoxia-inducible factor-1α and -2α in whole-mount prostate histology: relation with dynamic contrast-enhanced MRI and Gleason score.
abstract: The aim of this study was to investigate the association between the immunohistochemical expression of hypoxia-inducible factor (HIF)-1α and HIF-2α and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters Ktrans and kep in prostate cancer. Therefore, 15 patients with biopsy-confirmed prostate cancer underwent a pre-operative 3T DCE-MRI scan. Immunohistochemical analysis of HIF-1α and HIF-2α, and of CD31 for microvessel density (MVD) was performed. Tumor areas were delineated on whole-mount histopathological sections. Nuclear HIF expression was correlated with the quantitative DCE-MRI parameters Ktrans and kep, MVD and Gleason score. HIF expression was highly heterogeneous within tumors and between patients. Pronounced expression of HIF-2α was present, while HIF-1α expression was more limited. Larger tumors showed higher HIF-2α expression (p=0.041). A correlation between HIF-2α and Ktrans p5th was found (r=0.30, p=0.02), but no differences in Ktrans, kep and MVD were observed for different levels of HIF expression. HIF expression was not associated with Gleason score. In conclusion, in this whole-mount prostate cancer study, larger prostate tumors showed frequently high HIF-2α expression, suggesting that larger tumors are clinically most relevant. However, HIF-1α and HIF-2α were not correlated with DCE-MRI parameters. Given the pronounced expression of HIF-2α and independence of Gleason score, HIF expression may function as a biomarker to guide boost dose prescription.
authors.affiliation: Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands. a.borren@umcutrecht.nl
authors.forename: Alie
authors.initials: A
authors.lastname: Borren
authors.forename: Greetje
authors.initials: G
authors.lastname: Groenendaal
authors.forename: Petra
authors.initials: P
authors.lastname: van der Groep
authors.forename: Maaike R
authors.initials: MR
authors.lastname: Moman
authors.forename: Arto E
authors.initials: AE
authors.lastname: Boeken Kruger
authors.forename: Uulke A
authors.initials: UA
authors.lastname: van der Heide
authors.forename: Trudy N
authors.initials: TN
authors.lastname: Jonges
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Marco
authors.initials: M
authors.lastname: van Vulpen
authors.forename: Marielle E P
authors.initials: ME
authors.lastname: Philippens
mesh_terms: D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003287:Contrast Media / Q000493:pharmacokinetics*; D015870:Gene Expression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D003287:Contrast Media; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009942:Organometallic Compounds; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C090600:gadobutrol