Abstract

Central nervous system malignancies (CNSMs) are categorized among the most aggressive and deadly types of cancer. The low median survival in patients with CNSMs is partly explained by the objective difficulties of brain surgeries as well as by the acquired chemoresistance of CNSM cells. Flow Cytometry is an analytical technique with the ability to quantify cell phenotype and to categorize cell populations on the basis of their characteristics. In the current review, we summarize the Flow Cytometry methodologies that have been used to study different phenotypic aspects of CNSMs. These include DNA content analysis for the determination of malignancy status and phenotypic characterization, as well as the methodologies used during the development of novel therapeutic agents. We conclude with the historical and current utility of Flow Cytometry in the field, and we propose how we can exploit current and possible future methodologies in the battle against this dreadful type of malignancy.

Highlights

  • Vartholomatos, G.; Alexiou, G.A.; Faculty of Medicine, Neurosurgical Institute, School of Health Sciences, University of Ioannina, Haematology Laboratory-Unit of Molecular Biology, University Hospital of Ioannina, 45110 Ioannina, Greece; Department of Neurosurgery, University of Ioannina, 45110 Ioannina, Greece

  • The results were similar, since the DNA content in the benign tumors showed mainly diploid cell populations with a low proliferation index, while most the malignant Central nervous system malignancies (CNSMs), which were mainly gliomas, had aneuploid populations and/or a higher proliferation index [18]. Another interesting insight has been added by the study by Petersen et al, in which a rare CNSM has been characterized by both Flow Cytometry and cytogenetic analysis as hypodiploid, containing about 75% of the normal amount of DNA

  • In spite of the potential of clinical utility, Flow Cytometric analysis of DNA content and proliferation markers in CNSMs diagnosis have been scarcely used in clinical practice either as a diagnostic or a prognostic tool

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Summary

Introduction

Carcinogenesis is the step-by-step process through which normal cells acquire genetic and epigenetic alterations and transform into malignant cells that form a tumor mass. Cancer is among the leading causes of human mortality worldwide, with 18.1 million new cases and 9.5 million deaths in 2018 [1]. Central nervous system malignancies (CNSMs), including brain tumors (ICD codes C70-72) account for ~308,000 new cases and. Central nervous system tumors have been historically classified on the basis of the histology parameters, mainly as a result of the occurrence of malignancy from different brain tissues [2]. Glioblastoma (GBM) is the most common malignant primary brain tumor. The genetic heterogeneity and the diverse molecular pathology make it difficult to successfully treat the GBMs, and cells that are not eradicated eventually grow, and virtually all recurring tumors are resistant to both chemotherapy and radiotherapy [7].

Methods
Development of DNA Content Analysis
Intraoperative Flow Cytometry
Phenotypic Analysis
Flow Cytometry for Study of Anticancer Agent Efficacy
Findings
Conclusions
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