Shynkarenko T. Pathomorphological characteristics and diagnostic optimization of brain diffuse gliomas (immunohistochemical aspects)

The thesis is dedicated to the study of the diagnostic significance of the oncogenesis-dependent markers expression in diffuse gliomas and the establishment of basic and additional immunomorphological criteria for the Grade and type verification. Analysis of the regulation of cell cycle and DNA repair. The proliferation index (PI) of tumor cells is directly related to the malignancy degree (Grade) of gliomas (r=+0.756, p<0.05), but the statistical significance of the differences was recorded only between low-grade (Grade II) glial tumors vs anaplastic gliomas (p<0.0001) and vs glioblastomas (p<0.0001). The PI (Ki-67) was higher in astrocytic tumors (p=0.034), but when comparing gliomas belonging only to Grade II-III the difference was leveled (p=0.576), which indicated the inapplicability of this parameter for differentiation between tumors of astrocytic and oligodendroglial types. Analysis of intermediate filament expression. Glial tumors are characterized by a high level of GFAP expression, but oligodendroglial tumors were markedly less GFAP-immunoreactive compared to astrocytic (p=0.004), moreover, even with the exception of glioblastomas from the group of astrocytic tumors, this difference persisted (p=0.024). Also, diffuse gliomas did not demonstrate a Grade-dependent expression of GFAP (p=0.258). Analysis of the microvasculature parameters in diffuse gliomas. The endothelial PI, which characterizes the intensity of angiogenesis processes, was determined on the basis of the Ki-67-immunoreactivity of cells. There were significant differences in this parameter among tumors Grade II and Grade III (p=0.023). Astrocytic and oligodendroglial tumors Grade II-III were characterized by similar values of endothelial PI (p=0.274). Analysis of metabolic changes in diffuse gliomas. Analysis of the accumulation level of MMP3 (stromelysin-1) and MMP9 (gelatinase B / collagenase IV) made it possible to isolate groups of tumors with high and low proteolytic activity. A significant association of the accumulation of MMP and Grade tumors was recorded (p<0.05), with differences in low-grade vs anaplastic gliomas in MMP3 (p=0.018), and anaplastic tumors vs glioblastomas according to MMP9 (p=0.017). Astrocytic and oligodendroglial tumors were characterized by similar parameters of proteolytic activity, p> 0.05, and when switched off by glioblastomas the degree of similarity even increased for both enzymes.