B7-H3 is a new cancer-specific endothelial marker in clear cell renal cell carcinoma

Background: The purpose of this study was to validate B7-H3 as a new cancer-specific endothelial marker in clear cell renal cell carcinoma. Methods: B7-H3 expression patterns were compared between cancer and paired adjacent normal renal parenchyma by immunohistochemistry in paraffin-embedded specimens from 200 consecutive patients with clear cell renal cell carcinoma from January to December 2010. Four corpus luteum specimens were used as physiologic angiogenesis controls. B7-H3 messenger (m) RNA levels representing circulating endothelial cells were analyzed in 24 peripheral blood samples using real-time polymerase chain reaction. Collection and processing of tissue and peripheral blood samples was performed in compliance with the Declaration of Helsinki. Results: Cancer cell-specific expression of B7-H3 was detected in 19% of clear cell renal cell carcinoma specimens, and tumor vasculature B7-H3 expression was confirmed in 98% (196) of cases. A diffuse pattern of vascular B7-H3 expression was associated with multiple adverse clinical and pathologic features (P, 0.001). B7-H3 expression was not detected in paired adjacent normal renal parenchyma or vessels, or in luteal blood vessels. The B7-H3 mRNA level of circulating endothelial cells in peripheral blood was significantly higher in metastatic clear cell renal cell carcinoma (P, 0.001). Conclusion: This pilot study indicates that B7-H3 is a cancer-specific endothelial marker of potential importance for the development of tumor-specific, vascular-targeted therapies, and is a prognostic marker in clear cell renal cell carcinoma.