Expression and significance of B7-H3 and Tie-2 in the tumor vasculature of clear cell renal carcinoma

• Main Authors: Zhang X, Ji J, Zhang G, Fang C, Jiang F, Ma S, Hou J
• Format: Article
• Language: English
• Published: Dove Medical Press 2017-11-01
• Series: OncoTargets and Therapy
• Subjects: B7-H3; Tie-2; microvessel density; clear cell renal carcinoma; prognosis; angiogenesis
• Online Access: https://www.dovepress.com/expression-and-significance-of-b7-h3-and-tie-2-in-the-tumor-vasculatur-peer-reviewed-article-OTT

Xianyun Zhang,1,2 Jindong Ji,1 Guangbo Zhang,3 Chuntao Fang,4 Fujin Jiang,2 Song Ma,2 Jianquan Hou1 1Department of Urology, First Affiliated Hospital of Soochow University, Suzhou, 2Department of Urology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, 3Clinical Immunology Laboratory, First Affiliated Hospital of Soochow University, Suzhou, 4Department of Gynaecology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, Jiangsu, China Abstract: Tumor angiogenesis is required for tumor growth and metastasis, and the Ang/Tie-2 axis plays a pivotal role in angiogenesis. B7-H3, a new member of the B7 family of costimulatory molecules, has a critical function in the T-cell-mediated antitumor immune response, and abnormal tumor B7-H3 expression is frequently associated with a poor prognosis. However, the relationship between B7-H3 and angiogenesis in clear cell renal carcinoma (ccRCC) remains unclear. In this study, we used immunohistochemical methods to detect tumor vascular expression of B7-H3 and Tie-2 in tissue microarrays of 82 ccRCC patient samples. According to the results, B7-H3 is highly expressed in the tumor vascular endothelium of ccRCC and is associated with the ccRCC grade and tumor-node-metastasis (TNM) stage. Although vascular Tie-2 expression was also correlated with T stage and lymph node metastasis, it was not related to ccRCC grade or distant metastasis. The microvessel density (MVD) labeled by CD34 was correlated with tumor grade and TNM stage. Expression of B7-H3 and Tie-2 was positively correlated, and the levels were positively associated with the MVD. Additionally, immunofluorescence staining revealed coexpression of B7-H3 and Tie-2 in the vascular endothelia of ccRCC. Collectively, our findings suggest that expression of B7-H3 and Tie-2 in ccRCC tumor vasculature is closely related to the progression and prognosis of the disease. Furthermore, B7-H3 possibly promotes ccRCC angiogenesis through the Tie-2 pathway. Thus, B7-H3 might serve as an effective endothelial marker for ccRCC prognosis and become a promising target for ccRCC anti-angiogenic-targeted therapy. Keywords: B7-H3, Tie-2, microvessel density, clear cell renal carcinoma, prognosis, angiogenesis