Relationship between tumor vascularity and vascular endothelial growth factor as prognostic factors for patients with neuroblastoma [Odnos između tumorske vaskularnosti i vaskularnog endotelnog čimbenika rasta kao prognostičkih čimbenika kod bolesnika s neuroblastomom]

Jakovljević, Gordana and Čulić, Srđana and Stepan, Jasminka and Košuta, Iva and Seiwerth, Sven (2011) Relationship between tumor vascularity and vascular endothelial growth factor as prognostic factors for patients with neuroblastoma [Odnos između tumorske vaskularnosti i vaskularnog endotelnog čimbenika rasta kao prognostičkih čimbenika kod bolesnika s neuroblastomom]. Collegium Antropologicum, 35 (4). pp. 1071-1079. ISSN 0350-6134

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Abstract

Although the role of angiogenesis in tumor progression and response to treatment is generally well-characterized, for neuroblastomas clinical data regarding the contribution of angiogenesis and its predictive capacity remain unclear. The aim of this study was to evaluate whether tumor vascularity in the combination with expression of vascular endothelial growth factor (VEGF) represent prognostic factors for patients with neuroblastoma. Immunohistochemistry using anti-CD34 and anti-VEGF antibodies was used to analyze paraffin-embedded primary tumor tissues from 56 patients diagnosed with neuroblastoma. Tumor vascularity was estimated by calculating the tumor vascular volume fraction (TVVF), and VEGF expression was determined using semi-quantitative scoring. Statistical analyses including multivariate analysis were performed and compared with these two factors. Tumor vascularity had impact on survival of high VEGF expression neuroblastoma patients. Combination of high VEGF expression and TVVF value < or = 5% was independent predictor of overall survival (p-value = 0.0041, odds ratio (OR) (95% CI) = 8.67 (1.99-37.69) by the Cox proportional hazards model). This study revealed for the first time a group of extremely high-risk neuroblastoma with both high VEGF expression and poor vascularity. For these patients reduced rates of survival were observed (37% vs. 92.5%) (p < 0.0001). These patients did not experience a significant improvement following hematopoietic stem cell transplantation, and could be candidates for receiving novel therapies. These results indicate the importance of the mutual relationship between tumor vascularity and VEGF, because it gives better insight into the prognosis of patients with neuroblastoma.

Abstract in Croatian

Iako je utjecaj angiogeneze na tumorsku progresiju i liječenje dosta istražen, uloga angiogeneze i njeno prognostičko značenje kod neuroblastoma u kliničkoj praksi još je nejasno. Cilj ovog rada bio je istražiti da li kod neuroblastoma tumorska vaskularnost u kombinaciji s ekspresijom vaskularnog endotelnog čimbenika rasta (VEGF) predstavlja prognostički čimbenik rizika. Pomoću anti-CD34 i anti-VEGF antitijela učinjena je imunohistokemijska analiza tumorskog tkiva pohranjenog u obliku parafinskih kocki kod 56 bolesnika s neuroblastomom. Tumorska vaskularnost procijenjena je izračunavanjem tumorske vaskularne volumne frakcije (TVVF), a ekspresija VEGF-a semikvantitativnim bodovanjem. Učinjena je odgovarajuća statistička obrada uključujući i multivarijantnu analizu preživljenja. Tumorska vaskularnost utjecala je na preživljenje bolesnika s visokom VEGF ekspresijom.Visoka VEGF ekspresija u kombinaciji s TVVF < ili = 5% predstavljala je nezavisan prognostički čimbenik rizika (Coxova regresijska analiza, p-vrijednost=0,0041; omjer mogućnosti i 95% interval pouzdanosti =8,67 (1,99–37,69). Po prvi put otkrivena je skupina visoko rizičnih bolesnika čiji su tumori imali istovremeno visoku VEGF ekspresiju i malu vaskularnost. Kod tih bolesnika zapažen je nizak postotak preživljenja (37% naspram 92,5%) (p<0,0001). Oni nisu imali značajno poboljšanje preživljenja niti nakon transplantacije krvotvornih matičnih stanica, te bi takvi pacijenti mogli biti kandidati za primjenu novih metoda liječenja. Navedeni rezultati upućuju na važnost međusobnog odnosa tumorske vaskularnosti i VEGF-a, jer daje bolji uvid u prognozu bolesnika s neuroblastomom.

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