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Microbes & Immunity Characterizing low-grade CNS tumors

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

1. Introduction editions of the World Health Organization (WHO)
Classification of Tumors of the CNS, particularly the
Primary central nervous system (CNS) tumors represent 4 and 5 editions. In 2016, the WHO introduced
th
th
a broad category of malignancies with an incidence rate of integrated molecular and histological criteria for CNS
approximately 5 – 10 cases/100,000 individuals in India. tumor classification, which were further expanded in
Although they account for only 2 – 2.5% of all malignancy the 2021 edition with greater emphasis on molecular
cases, they are associated with significant morbidity and characterization. 9,10 The importance of these changes is
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mortality. A foundational cross-sectional study analyzing increasingly evident as tumor samples reveal molecular
39,509 cancer patient records from multiple hospitals and features that are either type- or grade-specific, or in
institutions in Kolkata, India, reported that 2.4% of all CNS some cases, shared across subtypes.
malignancies were primary CNS tumors, among which 60%
were gliomas, followed by meningioma, medulloblastomas, The molecular characterization of CNS tumors
primitive neuroectodermal tumors, and others. Another has advanced significantly with the identification
2
prospective epidemiological study reported that 59.6% of of key biomarkers. Ki-67 is a reliable marker of cell
all astrocytic tumors were high-grade astrocytomas, which proliferation, with expression levels markedly elevated in
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account for 38.7% of all astrocytic neoplasms in the study high-grade tumors. Matrix metalloproteinase (MMP)-2
population. More recently, a clinico-epidemiological study shows moderate expression in low-grade gliomas,
3
from Gauhati Medical College, Assam, India, reported reflecting limited invasiveness and an intact blood–brain
that 30% of all diagnosed brain tumors were glioblastoma barrier (BBB), but becomes significantly upregulated
multiforme, followed by 15% each for grade II and grade III in high-grade tumors, facilitating extracellular matrix
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astrocytomas. 4 degradation and invasive growth. Vascular endothelial
growth factor receptor 2 (VEGFR2) is minimally
CNS tumors are found to be more common in males
and frequently occur in individuals aged 40 – 60 years. expressed in low-grade tumors, indicating relatively
stable vascular architecture and limited angiogenesis,
Over two decades of surveillance have shown an increasing but is highly expressed in advanced CNS neoplasms,
trend in CNS tumor incidence in the Indian population, where it is related to pathological angiogenesis and
with overall poor due to the relatively high prevalence microvascular proliferation. Immune markers, such
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of gliomas despite recent therapeutic advancements. 1,2,5 as Cluster of Differentiation 11b (CD11b), a leukocyte/
Similarly, data from the Central Brain Tumor Registry of macrophage marker, and Iba1, a CNS macrophage/
the United States indicate that malignant brain tumors are microglia marker, play important roles in shaping the
higher in males, with a modest increase in overall survival tumor immune microenvironment. In high-grade CNS
in recent years; however, outcomes in elderly glioblastoma tumors, expression levels of CD11b and Iba1 increase
multiforme patients have demonstrated only marginal substantially, reflecting an altered immune landscape with
improvement. 6 greater invasion potential. Moreover, tumor-associated
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These findings suggest that the middle-aged Indian macrophages in high-grade tumors tend to polarize
population is more susceptible to glial-origin CNS toward the CD206 M2 phenotype, which promotes pro-
+
tumors than others, with prognosis heavily dependent tumorigenic activity – a feature largely absent in low-
on early diagnosis and treatment modules. Since grade tumors. DNA methyltransferase 1 (DNMT1) also
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radiological assessments are often limited by diagnostic displays grade-specific expression, remaining relatively
variability, and other non-invasive diagnostic methods low in low-grade tumors, consistent with stable DNA
remain elusive, molecular profiling has emerged as a methylation patterns. In contrast, DNMT1 is significantly
7
critical tool for identifying detailed tumor phenotypes – upregulated in high-grade tumors, contributing to
essential for accurate prognostication and personalized widespread CpG island hypermethylation and silencing
therapeutic interventions. Accordingly, molecular of tumor suppressor gene. Given the strong associations
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8
profiling is now prominently featured in the revised between these molecular markers, tumor phenotypes,
Volume 2 Issue 3 (2025) 131 doi: 10.36922/MI025190040