Expression of hypoxia-inducible factor-1α and -2α in whole-mount prostate histology: Relation with dynamic contrast-enhanced MRI and Gleason score

Borren,Alie; Groenendaal,Greetje; van der Groep,Petra; Moman,Maaike  R.; Boeken Kruger,Arto E.; van der Heide,Uulke  A.; Jonges,Trudy  N.; van Diest,Paul  J.; van Vulpen,Marco; Philippens,Marielle  E.P.

doi:10.3892/or.2013.2392

Expression of hypoxia-inducible factor-1α and -2α in whole-mount prostate histology: Relation with dynamic contrast-enhanced MRI and Gleason score

Authors:
- Alie Borren
- Greetje Groenendaal
- Petra van der Groep
- Maaike R. Moman
- Arto E. Boeken Kruger
- Uulke A. van der Heide
- Trudy N. Jonges
- Paul J. van Diest
- Marco van Vulpen
- Marielle E.P. Philippens
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Affiliations: Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands, Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands, Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands
Published online on: April 8, 2013 https://doi.org/10.3892/or.2013.2392
Pages: 2249-2254

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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.

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