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Vol. 24, Art. 7 (pp. 82-95)    |    2023       

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Comparative clinical and morphological study of the brain in various gliomas in association with epilepsy and inflammation

Mitrofanova L.B., Sokolov I.A., Vorobieva O.M., Sterkhova K.A., Ulitin A.Yu.

Almazov National Medical Research Centre

Brief summary

Epilepsy (E) is one of the most common neurological diseases. One of the factors of its development is inflammation, which is also associated with glial tumors, whose cells are capable of synthesizing a number of substances that modulate the activity of the inflammatory response [Galvão RP, Zong H., 2013]. Objective: to evaluate the contribution of inflammation to the development of cerebral gliomas and epilepsy Materials and methods: surgical material of 13 oligodendrogliomas (ODG) (of which 13 with E), 16 astrocytomas (A) Grade 2-4 (of which 12 with E and 4 without), 8 glioblastomas (GLB; of 3 of them with E and 5 without) and areas of the substance of the temporal lobe of 3 patients with focal cortical dysplasia IIb. A histological, immunohistochemical study was performed with antibodies to IDH1(R132H), Ki-67, p53, CXCR4, MHC1, CD3, CD16, CD68, CD117 and FISH in order to search for 1p19q codeletion. The tissue of the tumor and its perifocal zone (the zone of epileptic activity determined by electrocorticography) was studied. The average ratio of the number of cells (in %) with the expression of CD3, CD16, CD68, CD117 to the total number of cells in the field of view at x200 in 10 fields of view in each zone was determined. Results. The relative number of CD3+T-lymphocytes was statistically significantly lower in gliomas with IDH1 mutation (p=0.01), and the relative number of CD16+NK (p=0.04; 13 - 45 CD16+NK per field of view) and CD68+macrophages (p=0.01; 10-30 CD68+ cells per field of view) - significantly more in tumors compared to group E without them. In High-Grade gliomas, CD16+NK was significantly higher (30-55 in the field of view at x200) than in Low-Grade gliomas (p=0.002). Statistically significant in ODG Grade 2 there was a greater number of activated CD3+T-lymphocytes (8-29 per field of view; p=0.03) than in A Grade 2 and CD68+ macrophages (p=0.04) compared with High -Grade-gliomas. Significant correlations were found between the number of CD16+, CD68+cells and Ki-67 (r=0.49 and r=0.47, respectively), the number of CD16+ and CD68+cells (r=0.69), CD16+, CD68+ and CD3+cells (r=0.36 and r=0.52, respectively) in tumors. A significant correlation was also found between Grade of glioma and the number of CD68+cells (r=0.61). No significant difference was found in the number of inflammatory cells in tumors and in the peritumoral zone, and there was no correlation between the number of inflammatory cells and the presence of E, between the number of CD117+ telocytes (in %) and E. We found a dense network of intertwining elongated cells with long processes that expressed CD117 in the perifocal zone of ODG, A and GLB (in 62, 50, 50% of cases, respectively). Сonclusion Our study showed a greater dependence of the amount and composition of the inflammatory infiltrate on the tumor, the degree of its anaplasia (Grade) and proliferative activity, and not on the presence of E. A large number of CD16-positive NK cells in High-Grade gliomas, their significant correlation with the number of CD68+ microglia/macrophages and Ki-67 opens the way to personalized immunotherapy based on natural killer cells. We did not find a correlation between the number of CD117+ telocytes and E. Apparently, the main function of these cells in the tumor is regeneration. However, the electrophysiological properties of telocytes and the 3D structure of scars indicate the possibility of inducing epileptic activity.


Key words

epilepsy, gliomas, inflammation, immunohistochemical study

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