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DOI: 10.1055/s-0040-1708290
Does the expression of L-type amino acid transporters 1 (LAT1) differ between 18 F-FET-positve and 18 F-FET-negative gliomas?
Publication History
Publication Date:
08 April 2020 (online)
Ziel/Aim The uptake of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) in gliomas is suggested to be driven by an overexpression of L-type amino-acid transporter 1 (LAT1). However, 30 % of low- and 5 % of high-grade glioma do not present enhanced FET-uptake at primary diagnosis (FET-negative) - the pathophysiological basis for this phenomenon remains yet unclear. We aimed to assess the expression of LAT1 in a homogeneous group of FET-positive and FET-negative gliomas.
Methodik/Methods Newly diagnosed WHO grade II and III astrocytomas (IDH-mutant, no 1p/19q codeletion) were classified as either FET-negative (tumor-to-background ratio (TBR) <1.6) or FET-positive (TBR>1.6). LAT1 immunohistochemistry (IHC) was performed using a SLC7A5/LAT1 antibody. The percentage of LAT1-positive tumor cells (0, <25 %=1, <50 %=2, <75 %=3, >75 %=4) and the staining intensity (range: 0-3) was multiplied to an overall score (range 0-12) and correlated with the PET findings.
Ergebnisse/Results IHC is finalized in 18 cases, 50 cases are currently being analysed. 10 gliomas were FET-positive (4 WHO grade II, 6 WHO grade III), 8 were FET-negative (4 WHO grade II, 4 WHO grade III). FET-positive gliomas showed a significantly higher median amount of LAT1-positive tumor cells and a higher overall score than FET-negative gliomas (positive tumor cells=2.5 vs 1.5; p=0.034; overall score=4.5 vs 2.0; p=0.021). The staining intensity showed a trend towards higher values in FET-positive cases (2 vs 1; p=0.075). TBRmax showed a positive correlation with the amount of positive tumor cells (r=0.49; p=0.036) as well as the overall score (r= 0.50; p=0.041).
Schlussfolgerungen/Conclusions FET-negativity of gliomas is associated with a significantly smaller amount of LAT1-positive tumor cells compared to FET-positive gliomas within the same molecular genetic entity. The trend towards a lower LAT1-staining intensity in FET-negative tumor cells may further indicate a lower expression of LAT1 in the individual glioma cell, which is currently being evaluated in a significantly larger set of patients.
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