Expression of Ets‐1 in human clear cell renal cell carcinomas: Implications for angiogenesis

Expression of vascular endothelial growth factor (VEGF) has been reported in renal cell carcinoma (RCC), a highly angiogenic carcinoma. However, little or no information is available on the expression of Ets‐1, which is one of the target molecules of VEGF. In the present study, we examined the expression of Ets‐1 and VEGF in RCC by immunohistochemistry and reverse transcription–polymerase chain reaction (RT‐PCR), and correlations between expression and the microvessel density (MVD) were evaluated. Ets‐1 was immunolocalized to carcinoma cells and endothelial cells of the microvessels in clear cell RCC, but not in papillary RCC. Immunohistochemical Ets‐1 expression and MVD were significantly higher in clear cell RCC than in papillary RCC. Predominant mRNA expression of Ets‐1 in clear cell RCC was confirmed by RT‐PCR. The expression of Ets‐1 correlated directly with MVD in clear cell RCC. Hypoxic treatment upregulated the mRNA expression of Ets‐1 and VEGF in cell lines derived from clear cell RCC, suggesting that hypoxia is a key regulator for these molecules. These results demonstrate the expression of Ets‐1 in human clear cell RCC and suggest the possibility that Ets‐1 is involved in angiogenesis in clear cell RCC. (Cancer Sci 2006; 97: 875–882)