AccScience Publishing / MI / Online First / DOI: 10.36922/MI025190040
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ORIGINAL RESEARCH ARTICLE

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

Krishnendu Ghosh1,2,3 ,  Pritha Bhattacharjee2 ,  Anirban Ghosh1,4*
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1 Immunobiology Laboratory, Department of Zoology, Panihati Mahavidyalaya (West Bengal State University), Sodepur, West Bengal, India
2 Environmental Epigenomics Laboratory, Department of Environmental Science, University of Calcutta, Kolkata, West Bengal, India
3 Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
4 Cell Development and Immunobiology Laboratory, Department of Zoology, School of Sciences, Netaji Subhas Open University, Kolkata, West Bengal, India
MI, 025190040 https://doi.org/10.36922/MI025190040
Received: 8 May 2025 | Revised: 5 June 2025 | Accepted: 6 June 2025 | Published online: 16 July 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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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
Funding
This work was supported by the Council of Scientific and Industrial Research (CSIR), Government of India, through Project No. 37(1587)/13/EMR-II, and was partially supported by the Indian Council of Medical Research (ICMR) under project grant No. 61/8/2011- BMS, awarded to Dr. Anirban Ghosh as principal investigator.
Conflict of interest
The authors declare they have no competing interests.
References
  1. Dasgupta A, Gupta T, Jalali R. Indian data on central nervous tumors: A summary of published work. South Asian J Cancer. 2016;5(3):147-153. doi: 10.4103/2278-330X.187589

 

  1. Ghosh A, Sarkar S, Begum Z, et al. The first cross sectional survey on intracranial malignancy in Kolkata, India: Reflection of the State of the art in Southern West Bengal. Asian Pacific J Cancer Prev. 2004;5(3):259.

 

  1. Jalali R, Datta D. Prospective analysis of incidence of central nervous tumors presenting in a tertiary cancer hospital from India. J Neurooncol. 2008;87(1):111-114. doi: 10.1007/S11060-007-9487-Z

 

  1. Paul M, Goswami S, Goutham Raj C, Bora G. Clinico-epidemiological profile of primary brain tumours in North- Eastern region of India: A retrospective single institution study. Asian Pacific J Cancer Care. 2023;8(2):333-336. doi: 10.31557/apjcc.2023.8.2.333-336

 

  1. Yeole BB. Trends in the brain cancer incidence in India. Asian Pac J Cancer Prev. 2008;9(2):267-270.

 

  1. Miller KD, Ostrom QT, Kruchko C, et al. Brain and other central nervous system tumor statistics, 2021. CA A Cancer J Clin. 2021;71(5):381-406. doi: 10.3322/CAAC.21693

 

  1. Gao H, Jiang X. Progress on the diagnosis and evaluation of brain tumors. Cancer Imaging. 2013;13(4):466-481. doi: 10.1102/1470-7330.2013.0039

 

  1. Park SH, Won J, Kim SI, et al. Molecular testing of brain tumor. J Pathol Transl Med. 2017;51(3):205-223. doi: 10.4132/jptm/2017.03.08

 

  1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 2016;131(6):803-820. doi: 10.1007/s00401-016-1545-1

 

  1. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro Oncol. 2021;23(8):1231-1251. doi: 10.1093/neuonc/noab106

 

  1. Sincevičiūtė R, Vaitkienė P, Urbanavičiūtė R, Steponaitis G, Tamašauskas A, Skiriutė D. MMP2 is associated with glioma malignancy and patient outcome. Int J Clin Exp Pathol. 2018;11(6):3010-3018.

 

  1. Seyedmirzaei H, Shobeiri P, Turgut M, Hanaei S, Rezaei N. VEGF levels in patients with glioma: A systematic review and meta-analysis. Rev Neurosci. 2020;32(2):191-202. doi: 10.1515/revneuro-2020-0062

 

  1. Zheng Y, Graeber MB. Microglia and brain macrophages as drivers of glioma progression. Int J Mol Sci. 2022;23(24):15612. doi: 10.3390/ijms232415612

 

  1. Vidyarthi A, Agnihotri T, Khan N, et al. Predominance of M2 macrophages in gliomas leads to the suppression of local and systemic immunity. Cancer Immunol Immunother. 2019;68(12):1995-2004. doi: 10.1007/s00262-019-02423-8

 

  1. Rajendran G, Shanmuganandam K, Bendre A, Muzumdar D, Goel A, Shiras A. Epigenetic regulation of DNA methyltransferases: DNMT1 and DNMT3B in gliomas. J Neurooncol. 2011;104(2):483-494. doi: 10.1007/s11060-010-0520-2

 

  1. Zhao Y, Gan L, Ren L, Lin Y, Ma C, Lin X. Factors influencing the blood-brain barrier permeability. Brain Res. 2022;1788:147937. doi: 10.1016/j.brainres.2022.147937

 

  1. Alanen KA, Joensuu H, Klemi PJ. DNA ploidy and cell-cycle analysis in pancreatic and ampullary carcinoma: Flow cytometric study of formalin-fixed paraffin-embedded tissue. Virchows Arch A Pathol Anat Histopathol. 1991;419(3):255-256. doi: 10.1007/BF01626357

 

  1. Bready D, Placantonakis DG. Molecular pathogenesis of low-grade glioma. Neurosurg Clin N Am. 2019;30(1):17-25. doi: 10.1016/j.nec.2018.08.011

 

  1. Yrysov K, Arstanbekov N, Mamytov M, Akmataliev A, Turganbaev B, Vityala Y. Postoperative complications in patients with intracranial meningiomas who underwent surgery. Biomedicine. 2023;43(3):34-40. doi: 10.51248/.v43i3.2886

 

  1. Chang JH, Chang JW, Choi JY, Park YG, Chung SS. Complications after gamma knife radiosurgery for benign meningiomas. J Neurol Neurosurg Psychiatry. 2003;74(2):226-230. doi: 10.1136/jnnp.74.2.226

 

  1. Bertrand KC, Klimo P. Recent advancements in ependymoma: Challenges and therapeutic opportunities. Pediatr Neurosurg. 2023;58(5):307-312. doi: 10.1159/000530868

 

  1. Thotakura M, Tirumalasetti N, Krishna R. Role of Ki-67 labeling index as an adjunct to the histopathological diagnosis and grading of astrocytomas. J Cancer Res Ther. 2014;10(3):641-645. doi: 10.4103/0973-1482.139154

 

  1. Shivaprasad NV, Satish S, Ravishankar S, Vimalambike MG. Ki-67 immunostaining in astrocytomas: Association with histopathological grade - a South Indian study. J Neurosci Rural Pract. 2016;7(4):510-514. doi: 10.4103/0976-3147.188626

 

  1. Akyurek S, Chang EL, Yu TK, et al. Spinal myxopapillary ependymoma outcomes in patients treated with surgery and radiotherapy at M.D. Anderson cancer center. J Neurooncol. 2006;80(2):177-183. doi: 10.1007/s11060-006-9169-2.

 

  1. Snuderl M, Chi SN, De Santis SM, et al. Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas. J Neuropathol Exp Neurol. 2008;67(9):911-920. doi: 10.1097/NEN.0b013e318184f413

 

  1. Chen X, Li C, Che X, Chen H, Liu Z. Spinal myxopapillary ependymomas: A retrospective clinical and immunohistochemical study. Acta Neurochir (Wien). 2016;158(1):101-107. doi: 10.1007/s00701-015-2637-8

 

  1. Ghosh K, Ghosh S, Chatterjee U, Chaudhuri S, Anirban A. Microglial contribution to glioma progression: An immunohistochemical study in Eastern India. Asian Pac J Cancer Prev. 2016;17(6):2767-2773.

 

  1. Sato K, Kuratsu J, Takeshima H, Yoshimura T, Ushio Y. Expression of monocyte chemoattractant protein-1 in meningioma. J Neurosurg. 1995;82(5):874-878. doi: 10.3171/jns.1995.82.5.0874

 

  1. Lochhead JJ, Yang J, Ronaldson PT, Davis TP. Structure, function, and regulation of the blood-brain barrier tight junction in central nervous system disorders. Front Physiol. 2020;11:914. doi: 10.3389/fphys.2020.00914

 

  1. Yan D, Kowal J, Akkari L, et al. Inhibition of colony stimulating factor-1 receptor abrogates microenvironment-mediated therapeutic resistance in gliomas. Oncogene. 2017;36(43):6049-6058. doi: 10.1038/onc.2017.261

 

  1. Kvisten M, Mikkelsen VE, Stensjøen AL, Solheim O, Van Der Want J, Torp SH. Microglia and macrophages in human glioblastomas: A morphological and immunohistochemical study. Mol Clin Oncol. 2019;11(1):31-36. doi: 10.3892/mco.2019.1856

 

  1. Gutmann DH, Kettenmann H. Microglia/brain macrophages as central drivers of brain tumor pathobiology. Neuron. 2019;104(3):442-449. doi: 10.1016/j.neuron.2019.08.028

 

  1. Dubuc AM, Mack S, Unterberger A, Northcott PA, Taylor MD. The epigenetics of brain tumors. Methods Mol Biol. 2012;863:139-153. doi: 10.1007/978-1-61779-612-8_8

 

  1. Van Hooren L, Vaccaro A, Ramachandran M, et al. Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma. Nat Commun. 2021;12(1):4127. doi: 10.1038/s41467-021-24347-7

 

  1. Tang F, Wang Y, Zeng Y, Xiao A, Tong A, Xu J. Tumor-associated macrophage-related strategies for glioma immunotherapy. NPJ Precis Oncol. 2023;7(1):78. doi: 10.1038/s41698-023-00431-7

 

  1. Skouras P, Markouli M, Papadatou I, Piperi C. Targeting epigenetic mechanisms of resistance to chemotherapy in gliomas. Criti Rev Oncol Hematol. 2024;104:104532. doi: 10.1016/j.critrevonc.2024.104532

 

  1. Ghosh K, Ghosh S, Chatterjee U, Bhattacharjee P, Ghosh A. Dichotomy in growth and invasion from low- to high-grade glioma cellular variants. Cell Mol Neurobiol. 2022;42(7):2219-2234. doi: 10.1007/s10571-021-01096-1

 

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5):646-674. doi: 10.1016/j.cell.2011.02.013

 

  1. McClellan BL, Haase S, Nunez FJ, et al. Impact of epigenetic reprogramming on antitumor immune responses in glioma. J Clin Invest. 2023;133(2):e163450. doi: 10.1172/JCI163450

 

  1. Liu Y, Ali H, Khan F, Pang L, Chen P. Epigenetic regulation of tumor-immune symbiosis in glioma. Trends Mol Med. 2024;30(5):429-442. doi: 10.1016/j.molmed.2024.02.004

 

  1. Wang H, Diaz AK, Shaw TI, et al. Deep multiomics profiling of brain tumors identifies signaling networks downstream of cancer driver genes. Nat Commun. 2019;10(1):3718. doi: 10.1038/s41467-019-11661-4

 

  1. Ghosh A, Chaudhuri S. Tissue-free non-invasive diagnostic methodology for brain tumour: Present scenario and future direction. Biomedicine. 2019;44(1):39-45. doi: 10.51248/.v44i1.4045

 

  1. Heiden T, Castaños-Vélez E, Andersson LC, Biberfeld, P. Combined analysis of DNA ploidy, proliferation, and apoptosis in paraffin-embedded cell material by flow cytometry. Lab Invest. 2019;80(8):1207-1213. doi: 10.1038/labinvest.3780128
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Microbes & Immunity, Electronic ISSN: 3029-2883 Print ISSN: 3041-0886, Published by AccScience Publishing
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