title: An immunohistochemical study of the expression of the hypoxia markers Glut-1 and Ca-IX in canine sarcomas.
abstract: Tumor hypoxia has been associated with increased malignancy, likelihood of metastasis, and increased resistance to radiotherapy and chemotherapy in human medicine. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that is induced by tumor hypoxia and regulates the pathways involved in cellular response and adaptation to the hostile tumor microenvironment. HIF-1 induces transcription of different proteins, including Ca-IX and Glut-1, which are considered endogenous markers of chronic hypoxia in solid tumors in humans. In this study, sections from 40 canine sarcomas (20 histiocytic sarcomas and 20 low-grade soft-tissue sarcomas) were immunostained for these markers. Expression of Glut-1 was scored based on percentage of positive staining cells (0 = <1%; 1 = 1%-50%; 2 = >50%) and intensity of cellular staining (1 = weak; 2 = strong); Ca-IX was scored based on percentage of positive cells (0 = <1%; 1 = 1%-30%; 2 = >30%). Intratumoral microvessel density was measured using CD31 to assess intratumoral neoangiogenesis. Histiocytic sarcomas showed statistically significant higher Glut-1 immunoreactivity and angiogenesis than did low-grade soft-tissue sarcomas. Intratumoral microvessel density in histiocytic sarcomas was positively associated with Glut-1 immunoreactivity score. These findings suggest a potential role of hypoxia in the biology of these tumors and may provide a base for investigation of the potential prognostic use of these markers in naturally occurring canine tumors.
authors.affiliation: School of Veterinary Medicine, University of Glasgow, Bearsden, Glasgow, G611QH, UK. Email: erikaabbondati@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Abbondati
authors.forename: J
authors.initials: J
authors.lastname: Del-Pozo
authors.forename: T M
authors.initials: TM
authors.lastname: Hoather
authors.forename: F
authors.initials: F
authors.lastname: Constantino-Casas
authors.forename: J M
authors.initials: JM
authors.lastname: Dobson
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004285:Dogs; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D000860:Hypoxia / Q000662:veterinary; D007150:Immunohistochemistry / Q000662:veterinary; D055806:Microvessels; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000662:veterinary; D011379:Prognosis; D012189:Retrospective Studies; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery / Q000662:veterinary*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; D006023:Glycoproteins; D009363:Neoplasm Proteins
keywords: CD31; Ca-IX; Glut-1; canine; hypoxia; immunohistochemistry; sarcoma