Angiogenesis and radiological tumor growth in patients with glioblastoma

Abstract

BackgroundThe preoperative growth of human glioblastomas (GBMs) has been shown to vary among patients. In animal studies, angiogenesis has been linked to hypoxia and faster growth of GBM, however, its relation to the growth of human GBMs is sparsely studied. We have therefore aimed to look for associations between radiological speed of growth and microvessel density (MVD) counts of the endothelial markers vWF (Factor VIII related antigen) and CD105 (endoglin).MethodsPreoperative growth was estimated from segmented tumor volumes of two preoperative T1-weighted postcontrast magnetic resonance imaging scans taken ≥14 days apart in patients with newly diagnosed GBMs. A Gompertzian growth curve was computed from the volume data and separated the patients into two groups of either faster or slower tumor growth than expected. MVD counts of the immunohistochemical markers von Willebrand factor (vWF) (a pan-endothelial marker) and CD105 (a marker of proliferating endothelial cells) were assessed for associations with fast-growing tumors using Mann-Whitney U tests and a multivariable binary logistic regression analysis.ResultsWe found that only CD105-MVD was significantly associated with faster growth in a univariable analysis (p = 0.049). However, CD105-MVD was no longer significant when corrected for the presence of thromboses and high cellular density in a multivariable model, where the latter features were significant independent predictors of faster growth with respective odds ratios 4.2 (95% confidence interval, 1.2, 14.3), p = 0.021 and 2.6 (95% confidence interval, 1.0, 6.5), p = 0.048.ConclusionsMVDs of neither endothelial marker were independently associated with faster growth, suggesting angiogenesis-independent processes contribute to faster glioblastoma growth.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4768-9) contains supplementary material, which is available to authorized users.

CircSMARCA5 Regulates VEGFA mRNA Splicing and Angiogenesis in Glioblastoma Multiforme Through the Binding of SRSF1

“…Immunohistochemical sections were observed with a Zeiss Axioplan light microscope (CarlZeiss, Oberkochen, Germany). MVD assessment was performed as described by Weidner et al and Mikkelsen et al, with some modifications [44,45]. Briefly, vascular hotspots were identified on CD31 sections by a light microscope at 4× and 10× magnifications.…”

Silencing microRNA‐221/222 cluster suppresses glioblastoma angiogenesis by suppressor of cytokine signaling‐3‐dependent JAK/STAT pathway

“…Patients with glioblastoma can only survive for around 12–15 months, and only less than 5% patients can live for about 5 years with a 2‐year survival rate in only 13–26% patients (L. Zhang, Cao, Wei, Jiang, & Jia, ). Glioblastoma always displays characteristics like high proangiogenic factor secretion, rapid pretreatment growth, and extensive vascularity (Mikkelsen et al, ), and angiogenesis plays a critical role in the development of glioblastoma (Niola et al, ). Highly proliferative glioblastoma cells can induce angiogenic blood vessel sprouting, and several angiogenesis‐related factors are capable of driving endothelial blood vessel cell recruitment and proliferation by promoting the interaction between endothelial cells and tumor cells (Smits et al, ).…”

The histological representativeness of glioblastoma tissue samples

“…The immunohistochemical procedures for the staining of the proliferative marker Ki67/MIB-1 (monoclonal, Ki-67/MIB-1, 1:800 or 1:50, Dako, Glostrup, Denmark) and the endothelial marker CD105/endoglin (monoclonal, CD105/endoglin/SN6h, 1:50, Dako) have previously been accounted for [ 28 , 40 ]. The proliferative index (PI) of Ki67/MIB-1 was quantified as the percentage of distinctly positive tumor cells in hotspots in three HPFs, as previously described [ 40 ].…”