Association of specific vascular architecture with IDH1 status and young age.

<p>(A) Example of glomeruloid appearance of tumour vessels (arrows). Haematoxylin and eosin. (B) Tumour cell positivity for mutant IDH1 associated with glomeruloid vessels. RMH5984. (C) Contrast-enhanced T1-weighted images of patient RMH5984, showing an incompletely enhancing lesion (arrow). (D) Tumour vessels forming arcade-like structures (arrows). Haematoxylin and eosin. (E) All tumours with arcade-like vascular structures were negative for IDH1 mutation by immunohistochemistry (and direct sequencing). RMH6642. (F) Contrast-enhanced T1-weighted images of patient RMH6642, with pronounced ring-like enhancement (arrow). All histopathological images original magnification×200.</p

Differential patterns of vascularisation and necrosis.

<p>(A) Prominent vascularisation occurs around large necrotic areas of the tumour; (B) High expression of CD105 reflects active neovascularisation in these areas. RMH5967. (C) Regions with prominent pallisading necrosis were poorly vascularised; (D) Only scattered CD105-positive vessels were often observed. RMH5725 All images original magnification×100.</p

Distribution and clinical significance of predominant cell morphology in glioblastoma.

<p>(A) Pie chart showing proportion of tumours with predominant fibrillary (purple, 53.6%), gemistocytic (blue), 7.9%, giant cell (green, 3.9%), small cell (light green, 6.9%), oligodendroglial (yellow, 21.7%) and sarcomatous (orange, 5.8%) morphology. (B) Boxplot showing the age distribution of the morphological subtypes (C) Kaplan-Meier curve showing association of predominant cell morphology and clinical outcome (overall survival).</p

Patterns of vascularisation in glioblastoma.

<p>(A) Moderate increase of normal-looking or angulated/saw-like vessels positive for CD31. RMH5685 (B) Highly branching vessels positive for CD105. RMH5714 (C) CD31 staining and (D) CD105 staining highlighting increased vascular density and prominent microvascular proliferation in the transitional area between the highly infiltrating tumour edge and normal brain tissue. RMH6950 All images original magnification×100.</p

Distinct cell morphological types in clinical glioblastoma specimens.

<p>Examples of tumours are shown with predominant morphology classified as fibrillary (A, RMH5690, pleomorphic cells with pink cytoplasm and mitotic figures (arrows)), gemistocytic (B, RMH6716, cells with abundant glassy cytoplasm and eccentric nuclei (arrows)), giant cell (C, RMH6004, very large pleomorphic cells with hyperchromatic nuclei (arrows)), small cell (D, RMH5723, small cells with brisk mitotic activity (arrows)), oligodendroglial (E, RMH5970, ‘fried egg’ appearance of tumour cells (arrows)), and sarcomatous (F, RMH5966, disorganised fascicles of spindle cells (arrows)). All images original magnification×200, haematoxylin and eosin.</p

Clinicopathological correlates of predominant cell morphology in glioblastoma.

<p>Clinicopathological correlates of predominant cell morphology in glioblastoma.</p

Table of cases for which FISH results were available for all three genes.

<p>DNA copy number status, tumour receptor expression, diagnosis, age, IDH1 mutation status and MGMT methylation status are provided. Grey boxes, protein expression in conjunction with gene amplification for a given receptor. NA  =  not available.</p

Amplification of 4q12 genes in glioblastoma.

<p>(A) Representative FISH images showing individual amplification of <i>PDGFRA</i>, <i>KIT</i>, and <i>VEGFR2</i> in glioblastoma samples RMH6862, RMH6427 and RMH6881, respectively. Original magnification ×1000. (B) Pie charts showing the relative proportions of the predominant cellular morphology in glioblastoma samples for cases with <i>PDGFRA</i>, <i>KIT</i>, and <i>VEGFR2</i> amplification. Fibrillary, purple; gemistocytic, blue; giant cell, green; small cell, light green; oligodendroglial, yellow; and sarcomatous, orange. (C) Kaplan-Meier curves for the effect of amplification of <i>PDGFRA</i>, <i>KIT</i>, and <i>VEGFR2</i> on overall survival in glioblastoma patients. P values are given using the log-rank test for overall survival.</p

Differential patterns of 4q12 gene amplification.

<p>(A) Pie chart showing the relative proportions of distinct gene amplification subtypes in glioblastoma. All three genes, black; <i>PDGFRA</i> and <i>KIT</i>, purple; <i>PDGFRA</i>-only, red; normal copy number of all three genes, grey. (B) Boxplot showing the age distribution of the gene amplification subtypes. * p<0.05, t test. (C) Kaplan-Meier curves for the effect of gene amplification subtypes on clinical outcome.</p

miRNAs significantly up-regulated within the blastemal component of post-treatment high risk cases [Post-HR] when compared to post-treatment intermediate risk cases [Post-IR-Bl].

<p>miRNAs significantly up-regulated within the blastemal component of post-treatment high risk cases [Post-HR] when compared to post-treatment intermediate risk cases [Post-IR-Bl].</p