Abstract
Apart from its expression in benign and malignant prostate tissue, prostate specific membrane antigen (PSMA) was shown to be expressed specifically in the neovasculature of solid tumors. For gliomas only little information exists. Therefore, we aimed to correlate PSMA expression in gliomas to tumor metabolism by L-[S-methyl-11C]methionine (MET) PET and survival. Therefore, immunohistochemical staining (IHC) for isocitrate dehydrogenase 1-R132H (IDH1-R132H) mutation and PSMA expression was performed on the paraffin embedded tissue samples of 122 treatment-naive glioma patients. The IHC results were then related to the pre-therapeutic semiquantitative MET PET data and patients’ survival. Vascular PSMA expression was observed in 26 of 122 samples and was rather specific for high-grade gliomas ([HGG] 81% of glioblastoma multiforme, 10% of WHO grade III and just 2% of grade II gliomas). Significantly higher amounts of gliomas without verifiable IDH1-R132H mutation showed vascular PSMA expression. Significantly shorter median survival times were seen for patients with vascular PSMA staining in all tumors as well as HGG only. Additionally, significantly higher numbers of PSMA staining vessels were found in tumors with high amino acid metabolic rates. Vascular PSMA expression in gliomas was seen as a high-grade specific feature associated with elevated amino acid metabolism and short survival.
Highlights
The prostate specific membrane antigen (PSMA) is a type II transmembrane glycoprotein physiologically expressed in the kidney, proximal small intestine, and salivary glands
Distinct differences between high-grade (HGG) and low-grade gliomas (LGG) were seen with positive vessel staining for PSMA in 81% of GBM, 10% of WHO grade III and just 2% of grade II gliomas
Significantly higher PSMA staining vesselcounts were observed in wild-type gliomas (WT) compared to IDH1-R132H mutated gliomas (p < 0.001, WT: 13.3 vessels, IDH1-R132H mutated gliomas: 1.4 vessels)
Summary
The prostate specific membrane antigen (PSMA) is a type II transmembrane glycoprotein physiologically expressed in the kidney, proximal small intestine, and salivary glands. This transmembrane glycoprotein is known as glutamate carboxypeptidase II (GCPII), as folate hydrolase I (FOLH1) and as N-acetyl-L-aspartyl-L-glutamate peptidase I (NAALADase) in the CNS. A high PSMA expression in the endothelium of neovasculature of solid tumors but not in normal vessels has been observed [13,14,15,16,17,18] These conditions permit us to think about a theranostic approach in nuclear medicine for tumors other than prostate cancer
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