An Immunohistochemical Study of the Expression of the Hypoxia Markers Glut-1 and Ca-IX in Canine Sarcomas

• Published in: Veterinary pathology Vol. 50; no. 6; pp. 1063 - 1069
• Main Authors: Abbondati, E., Del-Pozo, J., Hoather, T. M., Constantino-Casas, F., Dobson, J. M.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.11.2013
• Subjects: Animals; Biomarkers, Tumor - metabolism; Dog Diseases - metabolism; Dog Diseases - pathology; Dog Diseases - surgery; Dogs; Glucose Transporter Type 1 - metabolism; Glycoproteins - metabolism; Hypoxia - veterinary; Immunohistochemistry - veterinary; Microvessels; Neoplasm Proteins - metabolism; Neovascularization, Pathologic - veterinary; Prognosis; Retrospective Studies; Sarcoma - metabolism; Sarcoma - pathology; Sarcoma - surgery; Sarcoma - veterinary; Treatment Outcome; CD31; hypoxia; Ca-IX; sarcoma; Glut-1; canine; immunohistochemistry
• ISSN: 0300-9858; 1544-2217
• DOI: 10.1177/0300985813486810

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.