Abbondati E, Del-Pozo J, Hoather T M, Constantino-Casas F, Dobson J M
School of Veterinary Medicine, University of Glasgow, Bearsden, Glasgow, G611QH, UK. Email:
Vet Pathol. 2013 Nov;50(6):1063-9. doi: 10.1177/0300985813486810. Epub 2013 Apr 29.
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.
在人类医学中，肿瘤缺氧与恶性程度增加、转移可能性增加以及对放疗和化疗的耐药性增加有关。缺氧诱导因子-1（HIF-1）是一种关键转录因子，由肿瘤缺氧诱导，调节参与细胞对恶劣肿瘤微环境反应和适应的途径。HIF-1诱导不同蛋白质的转录，包括碳酸酐酶IX（Ca-IX）和葡萄糖转运蛋白1（Glut-1），它们被认为是人类实体瘤中慢性缺氧的内源性标志物。在本研究中，对40例犬肉瘤（20例组织细胞肉瘤和20例低级别软组织肉瘤）的切片进行了这些标志物的免疫染色。根据阳性染色细胞百分比（0 = <1%；1 = 1%-50%；2 = >50%）和细胞染色强度（1 = 弱；2 = 强）对Glut-1的表达进行评分；根据阳性细胞百分比（0 = <1%；1 = 1%-30%；2 = >30%）对Ca-IX进行评分。使用CD31测量瘤内微血管密度，以评估瘤内新生血管形成。组织细胞肉瘤显示出比低级别软组织肉瘤在统计学上显著更高的Glut-1免疫反应性和血管生成。组织细胞肉瘤中的瘤内微血管密度与Glut-1免疫反应性评分呈正相关。这些发现提示缺氧在这些肿瘤生物学中可能发挥的作用，并可能为研究这些标志物在自然发生的犬肿瘤中的潜在预后用途提供基础。
