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犬乳腺恶性肿瘤中血管内皮生长因子受体-2(VEGFR-2)的表达:一项前瞻性生存研究

VEGFR-2 expression in malignant tumours of the canine mammary gland: a prospective survival study.

作者信息

Santos A, Lopes C, Gärtner F, Matos A J F

机构信息

Faculty of Veterinary Medicine, University Lusófona of Humanites and Technologies, Lisbon, Portugal.

Department of Molecular Pathology and Immunology, Biomedical Sciences Institute of Abel Salazar (ICBAS), University of Porto, Porto, Portugal.

出版信息

Vet Comp Oncol. 2016 Sep;14(3):e83-92. doi: 10.1111/vco.12107. Epub 2014 Jun 27.

DOI:10.1111/vco.12107
PMID:24976305
Abstract

Vascular endothelial growth factor receptor-2 (VEGFR-2) is the main receptor activated by vascular endothelial growth factor -A (VEGF-A) to promote tumour angiogenesis. Its clinical prognostic value has not been studied in canine mammary tumours (CMTs). Dogs with mammary cancer were enrolled in a survival study and the immunohistochemical expressions of VEGFR-2 and VEGF-A were analysed and associated with clinicopathological features. VEGFR-2 expression was associated with VEGF immunoreactivity in cancer cells, supporting the presence of an autocrine loop that may be involved in CMTs growth and survival. VEGFR-2 was also expressed by endothelial cells from tumour vasculature and positively associated with stromal matrix metalloproteinase-9 (MMP-9), suggesting the existence of a link between endothelial cells activation and up-regulation of matrix degrading proteins. Carcinosarcomas exhibited high VEGFR-2 expression suggesting that it may be one of the activated molecular pathways in this aggressive histological type and that VEGFR-2 inhibitors may constitute a potential treatment to improve the prognosis of these patients. Both VEGF and VEGFR-2 immunoreactivities were independent of patients' overall survival (OS) and disease-free survival (DFS).

摘要

血管内皮生长因子受体-2(VEGFR-2)是血管内皮生长因子-A(VEGF-A)激活的主要受体,可促进肿瘤血管生成。其临床预后价值尚未在犬乳腺肿瘤(CMT)中进行研究。患有乳腺癌的犬被纳入一项生存研究,分析了VEGFR-2和VEGF-A的免疫组化表达,并将其与临床病理特征相关联。VEGFR-2表达与癌细胞中的VEGF免疫反应性相关,支持可能参与CMT生长和存活的自分泌环的存在。VEGFR-2也由肿瘤血管的内皮细胞表达,并且与基质金属蛋白酶-9(MMP-9)呈正相关,表明内皮细胞激活与基质降解蛋白上调之间存在联系。癌肉瘤表现出高VEGFR-2表达,表明它可能是这种侵袭性组织学类型中激活的分子途径之一,并且VEGFR-2抑制剂可能构成改善这些患者预后的潜在治疗方法。VEGF和VEGFR-2免疫反应性均与患者的总生存期(OS)和无病生存期(DFS)无关。

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