Povezanost izraženosti IGFBP-2 i IGFBP-5 s pokazateljima angiogeneze te njihov prognostički značaj kod glioblastoma [Correlation of IGFBP-2 and IGFBP-5 expressions with the markers of angiogensis in glioblastoma and their prognostic significance]

Pažanin, Leo (2011) Povezanost izraženosti IGFBP-2 i IGFBP-5 s pokazateljima angiogeneze te njihov prognostički značaj kod glioblastoma [Correlation of IGFBP-2 and IGFBP-5 expressions with the markers of angiogensis in glioblastoma and their prognostic significance]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Glioblastoma is the most malignant, the best vascularised and the most frequent primary brain tumor. IGFBP-2 and IGFBP-5 through their IGFdependent and IGF-independent actions might have a significant role in anaplastic progression of astroglial tumors. The relationship between the expressions of these proteins and VEGF suggests the proangiogenic role for IGFBP-2 and antiangiogenic role for IGFBP-5. This is the basis for our hypothesis that IGFPB-2 expression positively and IGFBP-5 expression negatively correlate with the microvessel density and vascular patterns and that these correlations have prognostic impact in glioblastoma patients. To test this hypothesis we will immunohistochemically determine IGFBP-2 and IGFBP-5 expression, microvessel density and vascular patterns on 56 glioblastoma biopsy samples. Our results show IGFBP-2 expression in most glioblastomas (75%) and IGFBP- 5 expression in only 30% tumors. IGFBP-5 expression does not correlate with the microvessel density or with morphological pattern of neovascularisation and has no prognostic value. IGFBP- 2 expression correlates with the presence of palisading necrosis and with the presence of bizarre pattern of neovascularisation. IGFBP-2 immunoreactivity in more than 5% of tumor cells and the presence of palisading necrosis were prognostically significant in univariant analysis while in multivariant analysis only a patient’s age and the presence of palisading necrosis remained statistically significant.

Abstract in Croatian

Glioblastom je najzlocudniji, najbolje vaskularizirani i najcešci primarni tumor mozga. IGFBP-2 i IGFBP-5 proteini su koji, djelujuci samostalno ili u okviru IGF sustava, imaju znacajnu ulogu u zlocudnoj progresiji astroglijalnih tumora. Odnos izraženosti ovih proteina i VEGF-a upucuje na to da IGFBP-2 potice, a IGFBP-5 sprjecava angiogenezu. Na temelju toga može se pretpostaviti da izraženost IGFBP-2 pozitivno, a IGFBP-5 negativno korelira s gustocom novostvorenih tumorskih krvnih žila i morfološkim obrascem neovaskularizacije, te da ove korelacije u odnosu na preživljenje imaju prognosticki znacaj u oboljelih od glioblastoma. Kako bi se ispitala navedena hipoteza u ovom se radu na 56 patohistoloških uzoraka glioblastoma imunohistokemijskom metodom odredila izraženost IGFBP-2 i IGFBP-5, izmjerila se gustoca novostvorenih krvnih žila i odredio prevladavajuci obrazac neovaskularizacije. Dobiveni rezultati pokazuju da vecina glioblastoma pokazuje povecanu izraženost IGFBP-2 (75%), ali ne i IGFBP-5 (30%). Izraženost IGFBP-5 ne korelira ni s gustocom novostvorenih krvnih žila ni s morfološkim obrascem neovaskularizacije i nema prognostickog znacaja. Izraženost IGFBP-2 korelira s pojavom tumorskih pseudopalisada i s bizarnim obrascem neovaskularizacije. Statisticki znacajan utjecaj na preživljenje u univarijantnoj analizi imaju izraženost IGFBP-2 u >5% tumorskih stanica i prisutnost pseudopalisada, dok u multivarijantnoj analizi statisticki znacajan utjecaj na preživljenje imaju dob bolesnika i prisutnost pseudopalisada.

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