title: Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers in canine gliomas.
abstract: In human gliomas, tissue factor (TF) is overexpressed, associated with the grade of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen deposition and activation of the fibrinolytic system also play a role in tumour cell proliferation and angiogenesis. The first aim of the present study was to investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in canine glioma biopsies, graded according to the World Health Organization (WHO) classification of tumours of the central nervous system. The second aim was to investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas, as a potential histological marker of glioma type or grade of malignancy. An immunohistochemical study using antibodies against TF, fibrin/fibrinogen and D-dimers was performed with 24 glioma samples, including 15 oligodendrogliomas, 6 astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically analysed to determine whether there was any relationship between glioma type and grade of malignancy. All gliomas were moderate to strongly positive for TF and the staining score was significantly higher (P = 0.04) in high-grade (III or IV) than in low-grade (II) gliomas. Intra-tumoural fibrin/fibrinogen deposition was detected in all tumour biopsies assessed, and D-dimers were detected in 17/24 gliomas. IVT was a frequent finding, but was not linked to a specific glioma type or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma might be a suitable model for studying coagulation and fibrinolysis as potential therapeutic targets for human gliomas.
authors.affiliation: Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Fundació Hospital Clínic Veterinari, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Cristian
authors.initials: C
authors.lastname: de la Fuente
authors.affiliation: Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Martí
authors.initials: M
authors.lastname: Pumarola
authors.affiliation: Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Blasco
authors.affiliation: Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernández
authors.affiliation: Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Fundació Hospital Clínic Veterinari, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Viu
authors.affiliation: Departament de Medicina i Cirurgia Animal, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Fundació Hospital Clínic Veterinari, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. Electronic address: sonia.anor@uab.es.
authors.forename: Sònia
authors.initials: S
authors.lastname: Añor
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000209:etiology / Q000378:metabolism / Q000662:veterinary; D015415:Biomarkers; D004283:Dog Diseases / Q000209:etiology / Q000378:metabolism*; D004285:Dogs; D005337:Fibrin / Q000235:genetics* / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000235:genetics / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005910:Glioma / Q000209:etiology / Q000378:metabolism / Q000662:veterinary*; D007150:Immunohistochemistry / Q000662:veterinary; D009837:Oligodendroglioma / Q000209:etiology / Q000378:metabolism / Q000662:veterinary; D013030:Spain; D013925:Thromboplastin / Q000235:genetics* / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism / Q000662:veterinary*
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005337:Fibrin; D005340:Fibrinogen; D013925:Thromboplastin
keywords: Astrocytoma; Coagulation; Fibrinolysis; Immunohistochemistry; Oligodendroglioma