Cellular and molecular characteristics of low-grade central nervous system tumors revealing modulations in Ki-67/propidium iodide, MMP2, VEGFR2, and CD11b/Iba1: Analyses of post-operative samples

Abstract

The World Health Organization’s 2016 and 2021 classifications of central nervous system (CNS) tumors emphasize the integration of histopathological and molecular profiling for improved prognostic and therapeutic precision. Understanding the molecular hallmarks of low-grade CNS tumors is essential for enabling precision therapies and minimizing off-target effects while preventing malignant transformation. This study investigated key oncogenic features in surgically resected low-grade CNS tumors of varying cellular lineages and anatomical locations, alongside associated clinical metadata. Tumors were histologically classified and analyzed for molecular markers using immunohistochemistry, immunofluorescence microscopy, and flow cytometry. Assessed hallmarks included proliferation (Ki-67, propidium iodide index), invasiveness (matrix metalloproteinase [MMP]-2), neovascularization (vascular endothelial growth factor receptor 2 [VEGFR2], epigenetic modulation (DNA methyltransferase 1 [DNMT1], and immune microenvironment (Cluster of Differentiation 11b [CD11b], Iba1, silver-gold macrophage staining). Statistical analyses included t-tests, one-way ANOVA, and Kruskal-Wallis tests (p<0.05). In diffuse astrocytoma and myxopapillary ependymoma, a proliferation-invasion dichotomy was observed, with lower-proliferative ependymomas exhibiting higher MMP-2 expression. Astrocytomas exhibited elevated DNMT1 expression, indicative of increased epigenetic alterations. Immune profiling revealed tumor-specific differences: CD11b+ macrophages were more prominent in meningiomas, while Iba1+ microglia were enriched in astrocytomas, reflecting distinct immune microenvironments. Despite their low-grade classification, these tumors demonstrated hallmark cancer characteristics, variably expressed across astrocytoma, ependymoma, and meningioma. The combined assessment of Ki-67, MMP-2, VEGFR2, DNMT1, CD11b, and Iba1 provides a prognostically informative and therapeutically exploitable profile. These findings support the integration of molecular profiling into risk stratification and adjunctive treatment strategies to improve prognosis and reduce malignant progression in low-grade CNS tumors.

Keywords

Low-grade tumor / Astrocytoma / Ependymoma / Meningioma / Proliferation / Neo-vascularization / Invasion / Immune microenvironment