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      Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification

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          Abstract

          Background

          The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification.

          Methods

          Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts’ supervision, achieving an accuracy of 88.8% of overlay. Spearman’s correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples.

          Results

          Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks ( p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it ( p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2–2.5 times higher rCBV values in IDH-wildtype glioblastoma samples.

          Conclusions

          The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12885-021-09117-4.

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          Most cited references31

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          The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

          The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.
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            Microenvironmental regulation of tumour angiogenesis

            This Review discusses the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.
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              Tumor angiogenesis: molecular pathways and therapeutic targets.

              As angiogenesis is essential for tumor growth and metastasis, controlling tumor-associated angiogenesis is a promising tactic in limiting cancer progression. The tumor microenvironment comprises numerous signaling molecules and pathways that influence the angiogenic response. Understanding how these components functionally interact as angiogenic stimuli or as repressors and how mechanisms of resistance arise is required for the identification of new therapeutic strategies. Achieving a durable and efficient antiangiogenic response will require approaches to simultaneously or sequentially target multiple aspects of the tumor microenvironment.
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                Author and article information

                Contributors
                maaltor4@upv.es
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                6 January 2022
                6 January 2022
                2022
                : 22
                : 40
                Affiliations
                [1 ]GRID grid.157927.f, ISNI 0000 0004 1770 5832, Universitat Politècnica de València, Biomedical Data Science Laboratory, ITACA, ; 46022 Valencia, Spain
                [2 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, Oslo University Hospital, Department of Diagnostic Physics, ; 0424 Oslo, Norway
                [3 ]GRID grid.84393.35, ISNI 0000 0001 0360 9602, Health Research Institute Hospital La Fe, Department of Medical Oncology, Cancer Research Group, ; 46026 Valencia, Spain
                [4 ]GRID grid.84393.35, ISNI 0000 0001 0360 9602, Health Research Institute Hospital La Fe, Department of Medical Imaging, ; 46026 Valencia, Spain
                [5 ]GRID grid.84393.35, ISNI 0000 0001 0360 9602, Health Research Institute Hospital La Fe, Department of Pathology, ; 46026 Valencia, Spain
                Author information
                http://orcid.org/0000-0002-4935-3443
                Article
                9117
                10.1186/s12885-021-09117-4
                8734263
                34991512
                a75ab4fb-3196-4f9c-8ad7-69cbeac33653
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 20 July 2021
                : 15 December 2021
                Funding
                Funded by: national plan for scientific and technical research and innovation 2017-2020
                Award ID: PID2019-104978RB-I00
                Award Recipient :
                Funded by: h2020-sc1-2016-cnect project
                Award ID: 727560
                Award Recipient :
                Funded by: h2020-sc1-bhc-2018-2020
                Award ID: 825750
                Award Recipient :
                Funded by: programa estatal de promoción del talento y su empleabilidad en i+d+i
                Award ID: DPI2016-80054-R
                Award Recipient :
                Funded by: marie curiemarie skłodowska-curie grant agreement
                Award ID: 844646
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2022

                Oncology & Radiotherapy
                glioblastoma,relative blood volume,dsc perfusion,microvascular proliferation,idh mutation,histopathology

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