Background. Neuronal and mixed neuronal-glial tumors are rare brain tumors that are most commonly observed in pediatric patients. The main clinical manifestations are presented by epilepsy substantially affecting child’s physical and neurocognitive development.Objective: to assess short-term and long-term changes in seizure frequency and neurocognitive status in pediatric patients who underwent surgery for mixed neuronal-glial tumors.Material and methods. Thirty-eight pediatric patients underwent surgery for mixed neuronal-glial tumors at the Almazov Research Medical Centre within the period from 2008 to 2018. All patients had comprehensive diagnostic examination including clinical neurological examination, neuroimaging tests, electroencephalography and electrocorticography before and after surgery. The postoperative changes in the seizures rate were assessed by using the 1993, 1996 Engel classification. Neurocognitive status was evaluated using The Child Behavior Checklist (a component of the Achenbach System of Empirically Based Assessment).Results. During the postoperative period, 84% of patients were found to be seizure-free; 42.6% demonstrated no clinically relevant behavioral disturbances or social adaption issues after the surgery. However, 76% of children experienced poor concentration. In a long-term perspective, seizures reoccured in 25% of patients and were not associated with any magnetic resonance signs of tumor progression.Conclusion. A gross total resection of the brain tumor was the main factor that affected changes over time in seizure rate. Assessment of long-term changes over time has shown that the patients tended to retain concentration difficulties, which should be taken into account while planning school education programs.

Heat shock proteins (HSPs) constitute a large family of highly conserved proteins acting as molecular chaperones that play a key role in intracellular proteostasis, regulation of apoptosis, and protection from various stress factors (including hypoxia, thermal stress, oxidative stress). Apart from their intracellular localization, members of different HSPs families such as Hsp70 have been found to be localized on the plasma membrane of malignantly transformed cells, including multiforme glioblastoma (GBM). However, the role of the membrane-bound mHsp70 has not yet been elucidated in the pathophysiology of GBM. We have assessed the mHsp70 expression in biopsies obtained from neuro-oncological patients employing inverted confocal microscopy (Leica Microsystems) and CellVoyager CQ1 Benchtop High-Content Analysis System (Yokogawa). Live-cell imaging of the patient-derived biopsy revealed the increased cellular density of mHsp70-positive tumor cells particularly in the tissue along the tumor-brain margin (biopsy was derived 3 mm from contrast-enhancing margin and also within hyperintense FLAIR). Time-lapse analysis of the tumor sample further demonstrated the migration of mHsp70-positive cells into the surrounding culture medium. Subsequent high-powered multiplex immunofluorescence analysis (Akoya Biosystems Inc.) confirmed markedly increased single-cell infiltration of mHsp70(+) tumor cells (that were also co-immunofluorescently stained for SOX2, Nestin, and Oct4) in the normal brain tissues. In conclusion, expression of mHsp70 on the plasma membrane of tumor cells corresponds to the highly invasive potential of the GBM cells and recurrence of these tumors in neuro-oncological patients. This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Agreement № 075-15-2020-901). Citation Format: Maxim Shevtsov, Ruslana Tagaeva, Natalia Yudintceva, Danila Bobkov, Darya Goncharova, Alexander Kim, Evgeniy Fedorov, Anastasia Nechaeva, Anastasia Mihrina, Anna Patruhina, Vyacheslav Fedorov, Konstantin Samochernykh. Membrane-associated heat shock protein mHsp70 is involved in cancer cell invasion and tumor recurrence in malignant brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 504.

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