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

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.

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 (SUV_max). GLUT1, GLUT12 and HK2 expression were blindly scored after immunohistochemistry on specimens RP by three pathologists. Correlations between GLUT1, GLUT12 and HK2, and SUV_max were assessed using Spearman's rank correlation test. Survival probabilities were based on the Kaplan-Meier method.

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, SUV_max 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 SUV_max 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 SUV_max have been found.

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.