Abstract

Abstract Aggressive meningiomas are prone to recur despite GTR and eventually progress: they represent a challenge and are difficult to recognize at first diagnosis. SOX2 (Sex-determining region Y-box2) is a transcription regulator whose role is crucial for cell’s fate and maintenance of progenitor’s identity during embryogenesis, and homeostasis and regeneration in adult tissue through stem cell activity preservation. We reviewed meningioma cases surgically treated at Gemelli Hospital, Rome between 2014 and 2019. We included all patients with diagnosis of grade 3 meningiomas, both progressive and de novo, grade 2 with at least one surgical recurrence after GTR and benign grade 1 and grade 2 without recurrence at 10 and 5 years long follow-up respectively. SOX2 expression was evaluated through IHC and RT-PCR. Its role in predicting progression, recurrence, OS and PFS was investigated. 87 patients were included: 16 de novo grade 3 meningioma, 7 progressive grade 1, 13 progressive grade 2, 12 recurrent grade 2, 20 benign grade 1, 19 benign grade 2. The IHC method for SOX2 was validated by correlation between IHC score and mRNA levels (Spearman R=0.0398, p=0.001, AUC 0.87). Although SOX2 expression is related to WHO grade in the series, its status doesn’t change with progression. SOX2 expression at first surgery is related to risk of progression (p< 0,0001) and represents a grade independent prognostic factor for PFS and OS (PFS 38,41 months in positive cases vs not reached in negative cases; p< 0,0001; OS 173,9 months in positive cases vs not reached in negative cases; p=0,0001) and both in grade 1 and grade 2. Histomorphological criteria, cornerstone of the current WHO classification, are inadequate to predict aggressiveness. SOX2 expression since first diagnosis is able to point out meningiomas prone to recur and progress. SOX2 status could integrate current classification as molecular biomarker of stemness and aggressiveness.

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