Analysis of VEGF, Flt-1, Flk-1, and nestin in relation to astrocy-toma pathogenesis.

Konference: 2007 3. ročník Dny diagnostické, prediktivní a experimentální onkologie

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: 08. Prognostické a prediktivní faktory III

Číslo abstraktu: 037

Autoři: MUDr. Alice Hlobilková, Ph.D.; Mgr. Petra Knížetová, Ph.D.; prof. MUDr. Zdeněk Kolář, CSc.

Because of important role of angiogenesis in astrocytoma pathogenesis and progression, our immnunohistochemical study asssessed vascular endothelial growth factor (VEGF) and VEGF receptors (Flk-1, and Flt-1) expression in these tumours. Nestin is an intermediate filament protein expressed in neural stem cells, taking part in central nervous system (CNS) and CNS-derived tumours development. We investigated significance of VEGF, its receptors, and nestin expression in endothelial cells and in tumour astrocytes in correlation with tumour grade. The CD34 was used as a marker of endothelial cells in newly formed blood vessels. We used paraffin embedded astroglial tumour samples from 69 patients, which were divided into low grade astrocytomas (grade I-II) 32 samples and high grade astrocytomas (grade III IV) 37 samples. Mouse monoclonal antibodies against VEGF, Flk-1, nestin, CD34 and rabbit polyclonal serum against Flt-1were used, followed by standard indirect immunohistochemical method with Envision plus kit. A microwave generator was used for antigen retrieval. Both receptors, Flt-1 and Flk-1, were expressed in cytoplasm of tumour astrocytes and any significant differences were found between low and high grade groups. Expression of VEGF in cytoplasm was increased in high grade group with level of significancy 0.026. Nestin expression was found in cytoplasm of tumour astrocytes as well as endothelial cells. The level of its expression in both, tumour and endothelial cells, increased in high grade group with level of signicance 0.007 and 0.003. Higher expresion of VEGF, observed in high grade astrocytomas, might subsequently activate both PI3 K/PKB/Akt and MAPK pathways and participate on aggressiveness of tumours. Results concerning nestin detection indicated its possible role in tumour vascular development. Based on expression of nestin in tumour astrocytes we can deduce that nestin could also play a role in regulation of astrocytic proliferation.

This work was supported by grant IGA MZ CR NR/7828-3, IGA MZ CR NR/8370-3 and MSM 6198959216.

Datum přednesení příspěvku: 29. 11. 2007