{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:17:00Z","timestamp":1788308220851,"version":"build-2803163510"},"reference-count":25,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>The authors aimed to systematically investigate the expression and subcellular localization of estrogen receptors ER\u03b1 and GPER in meningioma and to evaluate the functional impact of estradiol on cell viability in common meningioma cell lines and primary patient-derived cultures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Tissue microarrays (TMAs) representing 120 patients (82 female, median age at diagnosis 57 years) with meningiomas (564 regions of interest) were analyzed using quantitative digital image analysis (QuPath) to evaluate nuclear and cytoplasmic receptor density. Subcellular localization was validated via immunofluorescence in meningeal and meningioma cell lines. Functional responsiveness to 17\u03b2-estradiol (E2) was assessed using in vitro cell viability assays with common meningioma cell lines Ben-Men-1, CH157-MN, IOMM-Lee, human meningeal cells, and primary cultured dura.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      GPER was ubiquitously expressed across the cohort, exhibiting both cytoplasmic and nuclear localization, whereas ER\u03b1 detection was comparatively limited. Multivariable linear regression analysis identified the anatomical location as a significant independent predictor of GPER expression. Non\u2013skull base tumors demonstrated higher GPER staining intensity compared with that of skull base tumors (nuclear, p = 0.013; cytoplasmic, p = 0.011). GPER staining intensity also varied across genomic alteration subgroups, with lower intensity observed in the\n                      <jats:italic>TRAF<\/jats:italic>\n                      7 \u00b1 other subgroup compared with\n                      <jats:italic>NF<\/jats:italic>\n                      2\/22\n                      <jats:italic>q<\/jats:italic>\n                      -loss tumors. In vitro experiments revealed a biphasic response to E2 in which low-dose exposure (1\u201310 pM) was frequently associated with reduced viability, whereas higher concentrations (10\u2013100 nM) increased cell viability. These effects varied across cell lines, with the\n                      <jats:italic>NF<\/jats:italic>\n                      2-loss CH157-MN meningioma cell line demonstrating the most pronounced increase in viability at 100 nM (adjusted p = 0.0002).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>These findings provide a systematic protein-level characterization of estrogen receptor expression in meningioma, identify GPER as a predominant receptor with expression patterns associated with tumor location and genomic subgroup, and lay the foundation for future mechanistic and translational studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2026.6.focus26267","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:01:11Z","timestamp":1787702471000},"page":"E13","source":"Crossref","is-referenced-by-count":0,"title":["Identification of G protein\u2013coupled estrogen receptor as an estrogen receptor associated with non\u2013skull base meningiomas"],"prefix":"10.3171","volume":"61","author":[{"given":"Danielle F.","family":"Miyagishima","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Yale University, New Haven; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Declan","family":"McGuone","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amos","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suleyman","family":"Coskun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University, New Haven; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batur","family":"Gultekin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University, New Haven; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavian","family":"Henegariu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University, New Haven; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketu","family":"Mishra-Gorur","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University, New Haven; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanyeri","family":"Barak","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University, New Haven; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Moliterno","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University, New Haven; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Gunel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University, New Haven; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"EClinicalMedicine","first-page":"103791","article-title":"Progestogen use and the risk of intracranial meningioma: a systematic review and meta-analysis","volume":"92","author":"Hudelist B","year":"2026","unstructured":"Hudelist B, Roux A, Huet-Mignaton E,  Progestogen use and the risk of intracranial meningioma: a systematic review and meta-analysis. 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