The Past, Present and Future of Flow Cytometry in Central Nervous System Malignancies

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.

Intraoperative Flow Cytometry for the Characterization of Gynecological Malignancies

“…This method offers numerous advantages, and can be successfully used for tumor diagnosis, as clonal expansion of cancer cells can be monitored as subpopulations with distinct genetic characteristics. It contributes towards precise intraoperative identification of tumor margins, offering the potential of complete removal, and is currently applied in brain [ 21 , 22 ], head-and-neck [ 23 , 24 ], breast [ 25 , 26 , 27 ], liver [ 28 ], pancreatic [ 29 ], and colorectal neoplasms [ 30 ]. To the best of our knowledge, the present study is the first application of iFC in the detection and characterization of cancer cells in gynecological malignancies.…”

“…Intraoperative flow cytometry (iFC) is a breakthrough technique enabling the cytometric analysis of DNA content/ploidy and cell-cycle distribution of cells acquired during surgical resection of tumors to characterize cancer cells and to evaluate the limits of resection, bridging the aforementioned gap between evaluation and surgery. This procedure has been applied by our team during central nervous tumor surgeries, and its significance has since been confirmed in several additional cancer types, including head-and-neck malignancies, breast cancer, hepatocellular cancer, pancreatic cancer, and colorectal cancer [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Intraoperative flow cytometry offers good diagnostic potential with high sensitivity and specificity, while a prognostic role is also suggested.…”

Accurate Characterization of Bladder Cancer Cells with Intraoperative Flow Cytometry

“…Intraoperative flow cytometry (iFC) is a rapid, highly sensitive and relatively inexpensive method with the potential of characterizing tumor biology and margin status, offering a potential of complete tumor removal. Our team has utilized intraoperative flow cytometry, originally for brain malignancies [ 20 , 21 , 22 , 23 ]. Based on the high diagnostic potential of iFC, the methodology has further been standardized and applied in several types of malignancy, including head and neck [ 24 , 25 ], breast [ 26 , 27 , 28 ], liver [ 29 ], pancreatic [ 30 ] colorectal [ 31 ], as well as gynecological neoplasms [ 32 ].…”

Touch Imprint Intraoperative Flow Cytometry as a Complementary Tool for Detailed Assessment of Resection Margins and Tumor Biology in Liver Surgery for Primary and Metastatic Liver Neoplasms

“…Τhe concept of intraoperative flow cytometry (iFC), was based on flow cytometric quantification of DNA content/ploidy and cell cycle distribution during surgery for cancer cell analysis and margin evaluation. The rationale of iFC offered the ability for intraoperative diagnosis, which serves as an alternative to pathology evaluation of tissue sections obtained during surgery of central nervous tumors (CNSTs) [ 11 ]. A modified rapid protocol for cell cycle analysis developed in the University Hospital of Ioannina (“Ioannina Protocol”) allowed the intraoperative characterization of intracranial lesions and their surgical margins in 6 min per sample.…”

“…The modified protocol is used for cancer cell characterization and margin detection during the excision of primary and metastatic liver neoplasms. The study is based on the established role of iFC by DNA-content and phenotypic analysis in CNSTs, breast-, and head-and-neck lesion-conserving surgeries, previously investigated by our research team [ 11 , 17 , 18 , 19 ].…”