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. 2021 Jan-Dec:20:1533033821990010.
doi: 10.1177/1533033821990010.

Hypoxia-Inducible Factor 2a Expression Is Positively Correlated With Gleason Score in Prostate Cancer

Dimitrios Pavlakis  1 , Spyridon Kampantais  1   2 , Konstantinos Gkagkalidis  1 , Victoras Gourvas  3 , Dimitrios Memmos  1 , Aikaterini Tsionga  1 , Georgios Dimitriadis  1 , Ioannis Vakalopoulos  1
Affiliations

Hypoxia-Inducible Factor 2a Expression Is Positively Correlated With Gleason Score in Prostate Cancer

Dimitrios Pavlakis et al. Technol Cancer Res Treat. 2021 Jan-Dec.

Abstract

Background: One of the main factors in response to hypoxia in the tumor microenvironment is the hypoxia-inducible factor (HIF) pathway. Although its role in other solid tumors, particularly renal cell carcinoma, has been sufficiently elucidated, it remains elusive in prostate cancer. The aim of the present study was to investigate the expression of main proteins involved in this pathway and determine the correlation of the results with clinicopathological outcomes of patients with prostate cancer.

Methods: The immunohistochemical expression of HIF-1a, HIF-2a and their regulators, prolyl hydroxylase domain (PHD)1, PHD2 and PHD3 and factor inhibiting HIF (FIH), was assessed on a tissue microarray. This was constructed from radical prostatectomy specimens, involving both tumor and corresponding adjacent non-tumoral prostate tissues from 50 patients with localized or locally advanced prostate cancer.

Results: In comparison with non-tumoral adjacent tissue, HIF-1a exhibited an equal or lower expression in 86% of the specimens (P = 0.017), while HIF-2a was overexpressed in 52% (P = 0.032) of the cases. HIF-1a protein expression was correlated with HIF-2a (P < 0.001), FIH (P = 0.004), PHD1 (P < 0.001), PHD2 (P < 0.001) and PHD3 (P = 0.035). HIF-2a expression was positively correlated with Gleason score (P = 0.017) and International Society of Urological Pathologists (ISUP) grade group (P = 0.022).

Conclusions: The findings of the present study suggest a key role for HIF-2a in prostate cancer, as HIF-2a expression was found to be correlated with Gleason score and ISUP grade of the patients. However, further studies are required to validate these results and investigate the potential value of HIF-2a as a therapeutic target in prostate cancer.

Keywords: FIH; Gleason score; HIF; hypoxia; prostate cancer.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
HIF-2a immunohistochemistry. A, Score 0: no staining. B, Score 1 out of 3 for intensity (weak) and 1 out of 4 for percentage (<25% of prostatic cells). C, Score 2/3 for intensity (moderate) and 3/4 for percentage (>50% and <75%). D, Score 3/4 for intensity (strong) and 4/4 for percentage (>75%).
Figure 2.
Figure 2.
Immunohistochemical stains for the selected antibodies in prostatic adenocarcinoma with various scores. A, FIH antibody scoring 2 out of 3 for intensity and 2 out of 4 for percentage (nuclear stain). B, HIF-1a antibody with 3/3 intensity and 4/4 percentage (cytoplasmic stain). C, PHD-1 antibody with 1/3 intensity and 1/4 percentage (cytoplasmic stain). D, PHD-2 antibody with 2/3 intensity and 2/4 percentage (mostly cytoplasmic stain). E, PHD-3 antibody with 0/3 intensity and 0/4 percentage (no stain).
Figure 3.
Figure 3.
Cumulative results of each protein expression for intensity of staining and percentage of immunostained epithelial prostatic cells.
Figure 4.
Figure 4.
Distribution of Gleason Score among patients with HIF-2a overexpression and patient with normal or low HIF-2a expression.
See this image and copyright information in PMC

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