Prostate-specific membrane antigen expression in meningioma

2072 Background: Meningioma is the most common CNS tumor, yet there is no effective therapy for relapsed/refractory meningioma after surgery and radiation therapy. Although most meningiomas follow a relatively benign course, some have a more aggressive course with rapid tumor growth, brain invasion, higher recurrence rates or extracranial metastasis. Prostate-specific membrane antigen (PSMA) is a transmembrane peptidase upregulated on endothelial cells of malignant solid tumors including glioblastoma and metastatic brain tumors, but not in normal vasculature. PSMA has been investigated as a therapeutic target and as a molecular imaging marker to monitor response to treatment and evaluate disease activity in PSMA-avid tumors. PSMA expression however has not been studied in meningioma. Methods: Archival tumor specimens (96 tumor samples: 58 WHO grade 1, 35 WHO grade 2, 3 WHO grade 3) from 69 patients were stained for H&E, PSMA and CD31 and slides were scanned (Leica Aperio AT2 whole slide image scanner). 37 of these samples were recurrent tumors and 13 had prior radiation therapy (intensity-modulated, Gamma knife, craniospinal). 21 of the 69 patients had paired samples of initial and recurrent tumors. QuPath was utilized as open access solution to machine learning generating raw data for PSMA, CD31, PSMA/CD31 ratio and PSMA/vasculature ratio. Paired t-test, unpaired t-test and ROC curves were used for statistical analysis. Results: PSMA expression was seen in all of the study samples. PSMA expression (p = 0.0147) was lower in grade 1 compared to grade 2 and 3 tumors, but not different among histologic subtypes. PSMA/vasculature ratio (p = 0.0015) was lower in grade 1 compared to grade 2 and 3 tumors. PSMA expression (p = 0.002) and PSMA/vasculature ratio (p = 0.0015) were higher in recurrent compared to non-recurrent tumors. PSMA expression (p = 0.0442) was higher in recurrent compared to initial tumors among paired samples. When comparing initial tumors of paired samples to non-recurrent tumors, ROC curves demonstrated CD31 expression (AUC:0.7278; p = 0.0008), PSMA/CD31 ratio (AUC:0.7843; p = < 0.0001) and PSMA/vasculature ratio (AUC:0.6256; p = 0.0328) to be predictors of tumor recurrence. Tumors with prior radiation therapy had higher PSMA/vascular ratio (p = 0.0439) compared to those without. Conclusions: PSMA is expressed in tumor vasculature of meningioma of any grade, increases at recurrence and persists with prior radiation therapy. Since it is present in meningioma of different grades and throughout the course of the disease, it could potentially be utilized as consistent diagnostic biomarker, relevant factor for risk of recurrence stratification and novel therapeutic target for these tumors.