Assessment of Gliomas’ Grade of Malignancy and Extent of Resection Using Intraoperative Flow Cytometry

Author:

Vartholomatos George12ORCID,Markopoulos Georgios S.12ORCID,Vartholomatos Eyrysthenis1,Goussia Anna C.34,Dova Lefkothea12,Dimitriadis Savvas1,Mantziou Stefania12,Zoi Vaso1,Nasios Anastasios125,Sioka Chrissa16,Kyritsis Athanasios P.1ORCID,Voulgaris Spyridon15,Alexiou George A.15ORCID

Affiliation:

1. Neurosurgical Institute, University of Ioannina School of Medicine, 45110 Ioannina, Greece

2. Haematology Laboratory, Unit of Molecular Biology and Translational Flow Cytometry, 45110 Ioannina, Greece

3. Department of Pathology, Ioannina University Hospital, 45500 Ioannina, Greece

4. Department of Pathology, German Oncology Center, 4108 Limassol, Cyprus

5. Department of Neurosurgery, University Hospital of Ioannina, 45500 Ioannina, Greece

6. Department of Nuclear Medicine, University Hospital of Ioannina, 45500 Ioannina, Greece

Abstract

Background: Intraoperative Flow Cytometry (iFC) is a novel technique for the assessment of the grade of malignancy and the diagnosis of tumor type and resection margins during solid tumor surgery. Herein, we set out to analyze the role of iFC in the grading of gliomas and the evaluation of resection margins. Material and Methods: iFC uses a fast cell cycle analysis protocol (Ioannina Protocol) that permits the analysis of tissue samples within 5–6 min. Cell cycle analysis evaluated the G0/G1 phase, S-phase, mitosis, and tumor index (S + mitosis phase fraction) and ploidy status. In the current study, we evaluated tumor samples and samples from the peripheral borders from patients with gliomas who underwent surgery over an 8-year period. Results: Eighty-one patients were included in the study. There were sixty-eight glioblastoma cases, five anaplastic astrocytomas, two anaplastic oligodendrogliomas, one pilocytic astrocytoma, three oligodendrogliomas and two diffuse astrocytomas. High-grade gliomas had a significantly higher tumor index than low grade gliomas (median value 22 vs. 7.5, respectively, p = 0.002). Using ROC curve analysis, a cut-off value of 17% in the tumor index could differentiate low- from high-grade gliomas with a 61.4% sensitivity and 100% specificity. All low-grade gliomas were diploid. From the high-grade gliomas, 22 tumors were aneuploid. In glioblastomas, aneuploid tumors had a significantly higher tumor index (p = 0.0018). Twenty-three samples from glioma margins were evaluated. iFC verified the presence of malignant tissue in every case, using histology as the gold standard. Conclusion: iFC constitutes a promising intraoperative technique for glioma grading and resection margin assessment. Comparative studies with additional intraoperative adjuncts are necessary.

Funder

European Regional Development Fund of the European Union and Greek national funds

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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