Prognostic implications of CD95 receptor expression in clear cell renal carcinomas

The CD95 (Apo-1/Fas) receptor-ligand system is a key regulator of apoptosis. Down-regulation of CD95 receptor and up-regulation of CD95 ligand has been reported in a variety of human tumors and is thought to confer a selective survival advantage. To explore the relevance of the CD95 system for tumor progression and prognosis in clear cell renal cell carcinomas (RCCs), we analyzed CD95 receptor and ligand expression in formalin-fixed tissue from 149 clear cell RCCs by immunohistochemistry. CD95 ligand expression could not be detected in nonneoplastic tubule epithelia and in clear cell RCCs. In contrast, CD95 receptor expression was found in the great majority of clear cell RCCs, and no down-regulation of CD95 receptor protein was evident when compared with nonneoplastic tubule epithelia. Although a significant increase (P = 0.004) of CD95 receptor expression was evident from well-differentiated (G1) to poorly differentiated (G3) RCCs, CD95 receptor expression was not correlated with tumor stage or survival of RCC patients. In conclusion, clear cell RCCs differ from other types of human cancer by their failure to down-regulate CD95 receptor expression or up-regulate CD95 ligand expression during tumor progression. These ex vivo observations suggest that down-regulation of CD95 receptor expression may not provide an additional selective growth advantage to RCC cells and thus further confirm our previous in vitro observations on a functional impairment of CD95-mediated apoptosis in RCC.