Odnos tumorske neoangiogeneze i vaskularnog endotelnog čimbenika rasta, te njihov značaj u bolesnika s neuroblastomom [Relationship between tumor neoangiogenesis and vascular endothelial growth factor, and their significance as prognostic factors in patients with neuroblastoma]

Jakovljević, Gordana (2010) Odnos tumorske neoangiogeneze i vaskularnog endotelnog čimbenika rasta, te njihov značaj u bolesnika s neuroblastomom [Relationship between tumor neoangiogenesis and vascular endothelial growth factor, and their significance as prognostic factors in patients with neuroblastoma]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Background: Although angiogenesis correlates with advanced tumor stage and plays an important role in determining the tumor response to treatment in general, clinical data on the prediction significance in neuroblastoma angiogenesis are still insufficient. The aim of this research was to evaluate the significance of VEGF expression and tumor angiogenesis in prognosis of neuroblastoma patients. Hypothesis and Objectives: VEGF-A expression and tumor vascularity are the prognostic risk factors in patients with neuroblastoma. High VEGF-A expression correlates with high tumor vascularity, and their relationship is essential for assessing the aggressiveness of tumor phenotype. The aim of this study was to determine the significance of vascular parameters and the expression of VEGF-A in survival prediction of neuroblastoma patients. Materials and Methods: VEGF expression and tumor angiogenesis was determined by immunohistochemistry using anti-VEGF and anti-CD34 antibody in paraffin embedded primary tumor tissue from 56 neuroblastoma patients. VEGF expression was estimated using semiquantitative score. Tumor angiogenesis parameters were analyzed using computer measurements. Results: VEGF expression correlated with the stage and survival. Patients with high VEGF expression had worse survival, and all patients with low VEGF expression have survived. The morphometric values of the majority of vascular parameters were not associated with VEGF expression. Tumor vascularity was important for high-risk patients’ survival and poor vascularity was accompanied by short survival. Unfavorable outcome was also found in patients with high VEGF expression and poor tumor angiogenesis. Hematopoietic stem cells transplantation increased the survival of high-risk patients with high VEGF expression, and extensive tumor vascularity. Conclusions: VEGF score proved to be useful, and could be used in a routine diagnostic practice. This study confirmed the significance of VEGF expression and tumor angiogenesis for the prognosis of patients with neuroblastoma. These factors should be 119 analyzed in a joint context, because it provides the most valuable prognostic results. They could contribute to the assessment of high risk neuroblastoma patients, as well as assessing the indications for transplantation and the introduction of inhibitors of tumor angiogenesis.

Abstract in Croatian

Uvod: Iako je poznato da tumorska angiogeneza korelira s uznapredovalim tumorskim stadijem i igra vaţnu ulogu u preţivljenju bolesnika, klinički podaci o prognostičkom značenju angiogeneze kod neuroblastoma su još nedostatni. Hipoteza i ciljevi: Ekspresija VEGF-A i tumorska vaskularnost su prognostički čimbenici rizika kod bolesnika s neuroblastomom. Visoka ekspresija VEGF-A korelira s visoko izraţenom tumorskom vaskularnošću, a njihov meĎusobni odnos bitan je za procjenu agresivnosti tumorskog fenotipa. Cilj ovog istraţivanja je objektiviziranje značenja vaskularnih parametara i ekspresije VEGF-A za prognozu bolesnika s neuroblastomom. Materijali i metode: Analizirano je 56 bolesnika s postavljenom dijagnozom neuroblastoma. Ekspresija VEGF-A i tumorska angiogeneza analizirane su pomoću anti-VEGF i anti-CD34 protutijela imunohistokemijskom metodom iz tumorskog tkiva koje je uzeto kod postavljanja dijagnoze. Ekspresija VEGF-A procijenjena je pomoću semikvantitativnog zbira bodova, a parametri tumorske angiogeneze analizirani su pomoću kompjuterskog mjerenja. Rezultati: Ekspresija VEGF-A korelirala je sa stadijem bolesti i preţivljenjem. Bolesnici s visokom ekspresijom VEGF-A imali su lošije preţivljenje, a svi bolesnici s niskom ekspresijom VEGF-A su preţivjeli. Morfometrijske vrijednosti većine vaskularnih parametara nisu korelirale s ekspresijom VEGF-A. Tumorska vaskularnost se pokazala značajna kod visoko rizičnih bolesnika, a slabija angiogeneza bila praćena lošijim preţivljenjem. Loše preţivljenje je otkriveno i kod bolesnika s visokom ekspresijom VEGF-A i slabom angiogenezom. Transplantacija krvotvornih matičnih stanica povećavala je preţivljenje visokorizičnih bolesnika s visokom ekspresijom VEGF-A i velikom tumorskom vaskularnošću. Zaključak: Ekspresijski zbir bodova VEGF-A pokazao se koristan, te bi ga bilo dobro upotrebljavati u rutinskoj dijagnostici. PotvrĎeno je značenje VEGF-A i tumorske angiogeneze za prognozu bolesnika s neuroblastomom. Navedene čimbenike treba analizirati u zajedničkom kontekstu jer to daje prognostički najvrijednije rezultate. Oni mogu pridonijeti procjeni visoko rizičnih bolesnika s neuroblastomom, kao i procjeni indikacije za transplantaciju i uvoĎenje antiangiogene terapije.

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