GLUT1 expression in high-risk prostate cancer: correlation with 18F-FDG-PET/CT and clinical outcome

Abstract

Background

Tumour 18F-FDG-uptake is of prognostic value in high-risk and metastatic prostate cancer (PCa). The aim of this study is to investigate the underlying glucose metabolism mechanisms of 18F-FDG-uptake on PET/CT imaging in PCa.

Methods

Retrospective analysis was conducted for 94 patients diagnosed with a Gleason sum ≥8 adenocarcinoma of the prostate at biopsy between July 2011 and July 2014 who underwent 18F-FDG-PET/CT imaging before radical prostatectomy (RP). 18F-FDG-uptake in primary lesion was measured by a blinded reader using maximum standardised uptake value (SUVmax). GLUT1, GLUT12 and HK2 expression were blindly scored after immunohistochemistry on specimens RP by three pathologists. Correlations between GLUT1, GLUT12 and HK2, and SUVmax were assessed using Spearman’s rank correlation test. Survival probabilities were based on the Kaplan–Meier method.

Results

With a median follow-up of 4.5 years, 56% (n = 53) of patients had biochemical recurrence (BCR), 7% (n = 7) progressed to castration-resistant prostate cancer (CRPC) disease, 13% (n = 12) developed metastasis and 6% (n = 6) died. Correlation was found between GLUT1 expression and SUVmax level (r = 0.25, p = 0.02). In addition, SUVmax was significantly higher in tumours with high GLUT1 expression (n = 17, 5.74 ± 1.67) than tumours with low GLUT1 expression (n = 71, 2.68 ± 0.31, p = 0.004). Moreover, a significant association was found between GLUT1 expression levels and SUVmax level (p = 0.005), lymph node status (p = 0.05), volume of cancer (p = 0.01), CRPC disease progression (p = 0.02) and metastasis development (p = 0.04). No significant difference between GLUT12 and HEX2 expression and SUVmax have been found.

Conclusions

GLUT1 expression in PCa tumours correlates with 18F-FDG-uptake and poor prognostic factors. These results suggest that this transporter is involved in the molecular mechanism of 18F-FDG-uptake in high-risk PCa and raise interest in targeting metabolic dependencies of PCa cells as a selective anticancer strategy.

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Fig. 1: 18F-FDG PET/CT transaxial images and immunohistochemistry expression levels of GLUT1, GLUT2 and HK2 in high grade prostate cancer.
Fig. 2: Correlation between GLUT1, GLUT12 and HK2 with SUVmax.
Fig. 3: Kaplan-Meier curves of survival according to GLUT1 expression level.

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Acknowledgements

We thank David Simonyan for his kind assistance with data statistics.

Author information

SM, HH, JR and FP designed the study. EL and MB revised patient’s data. HH, DL and HB performed the IHC. SM, VL and JR interpreted IHC slides. CRG and AC performed statistical analysis. JMB and FAB analysed PET/CT images. CRG build the figures and wrote the first draft of the manuscript. SM, HH, AC, BN and FP edit and revised the paper. FP supervised the study.

Correspondence to Frédéric Pouliot.

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Meziou, S., Ringuette Goulet, C., Hovington, H. et al. GLUT1 expression in high-risk prostate cancer: correlation with 18F-FDG-PET/CT and clinical outcome. Prostate Cancer Prostatic Dis (2020). https://doi.org/10.1038/s41391-020-0202-x

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