P13.03.B MCM2 HIGHLIGHTS A SUBSET OF AGGRESSIVE MENINGIOMAS WITH ENHANCED PROLIFERATION

Abstract BACKGROUND While most meningiomas are benign with favorable outcomes, a subset demonstrates high proliferative capacity and follows a lethal clinical course. To predict the postoperative behavior of meningiomas and refine our treatment strategy, we focused on minichromosome maintenance protein 2 (MCM2), a marker of cell proliferation, and investigated the clinical and molecular differences between tumors with high versus low MCM2 immunohistochemical positivity. MATERIAL AND METHODS We performed MCM2 immunohistochemistry on surgical specimens from 36 patients with meningiomas treated at our institution with tumor resection followed by radiotherapy. Cases were dichotomized into MCM2-high and MCM2-low groups based on a 35% positivity cutoff, and progression-free survival (PFS) was compared between groups. In addition, RNA sequencing was conducted in 14 selected cases to assess differences in gene expression profiles between the groups. These findings were validated using public transcriptomic data from the Meningioma (University of Toronto, Nature 2021) cohort. Furthermore, ultrastructural analysis was performed using electron microscopy on high-grade meningioma tissues to investigate intracellular features associated with aggressive behavior. RESULTS The MCM2-high group showed significantly shorter PFS compared to the low group (p < 0.0001), indicating a poorer prognosis. MCM2 mRNA levels were significantly higher in the high group (p = 0.000127), and genes related to cell division and cell cycle regulation were also upregulated. These transcriptomic trends were consistent with findings from the public dataset. These results suggest that elevated MCM2 expression reflects enhanced proliferative activity and contributes to poor clinical outcomes. Additionally, electron microscopy revealed abundant morphologically abnormal mitochondria in high-grade tumors, implying a cancer-like metabolic phenotype. CONCLUSION High MCM2 positivity serves as a surrogate marker for increased mitotic activity and poor prognosis in meningiomas. Moreover, energy metabolism in high-grade meningiomas may align with that of malignant tumors, highlighting a potential therapeutic target. SUPPORT This study was funded by the Japan Society for the Promotion of Science KAKENHI grant (25K18859).