Abstract 476P
Background
Androgen receptor (AR) is a steroid receptor gene located on X chromosome at Xq11–12 and is overexpressed in several solid tumors representing a potential therapeutic target. AR activity and expression is mediated by several genes located on the X chromosome such as: FLNA, UXT and the MAGE family genes (MAGEA1, MAGEA2, MAGEA3, MAGEA9, MAGEA11, MAGEC1, MAGEC2). In this study we investigated the role of AR expression and regulation in patients with gliomas.
Methods
Adult patients with pathologically confirmed grade 2 or 3 or 4 adult-type diffuse gliomas (according to the WHO 2021 classification) treated in our Institution have been evaluated. The AR expression and regulatory status was investigated by Immunohistochemistry (ICH) and gene methylation analysis.
Results
Overall, samples from 50 adult patients have been evaluated. 26 patients were males and 24 were females, with a median age of 51.9 years (range 26.3-76.9). The AR expression detected by ICH was predominant in males (p=0.04), in glioblastoma (GBM) patients IDH-wild type (compared to lower grade adult-type diffuse gliomas, p=0.04), and in astrocytoma (compared to oligodendrogliomas IDH-mutant and 1p19q codeleted, p=0.02). There was an association between AR expression and MGMT methylation, being AR expression more frequently detected in MGMT unmethylated gliomas (p=0.02). AR was found hypomethylated in cases with immunohistochemical positivity AR (Kruskal Wallis < 0.05). UXT, MAGEA1, and MAGEA1-11 were hypermethylated in AR-positive gliomas (Kruskal Wallis < 0.05). AR hypomethylation was deeper in GBM (Kruskal Wallis <0.05).
Conclusions
AR expression is higher in MGMT unmethylated tumors, astrocytoma, glioblastoma IDH-WT, and male patients. The methylation of AR regulatory genes on the X chromosome mediates AR expression. These data indicate that the AR pathway could be important in adult-type diffuse gliomas suggesting a potential role of antiandrogen therapies in these patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
IRCCS Istituto delle Scienze Neurologiche di Bologna.
Funding
CARISBO.
Disclosure
All authors have declared no conflicts of interest.
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