Significance of Fas expression alteration during tumor progression of renal cell carcinoma

Abstract

In order to characterize the alteration of apoptotic regulatory molecule expression during tumor progression of renal cell carcinoma (RCC), we compared the expression between tumor and normal tissues, and evaluated the relationship of the expression in tumors with pathological and clinical characteristics. Competitive reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) allowed the determination of Fas and bcl-2 mRNA and protein expression in surgically resected tumor and normal tissue of 50 RCC. The mRNA expression of Fas and bcl-2 in RCC was significantly reduced compared to that in normal tissues. An IHC analysis was supportive of the RT-PCR results. In terms of relationships with pathological and clinical characteristics, the mRNA and protein expression of Fas in high-stage or high-grade tumors was significantly higher than that in low-stage or low-grade tumors. Moreover, a statistically poor prognosis was observed in tumor cases expressing a high amount of mRNA. In bcl-2 analysis, the mRNA and protein expression was significantly reduced in clear cell tumors compared to chromophobe cell tumors. It is suggested that the reduced expression of Fas and bcl-2 in RCC compared with the expression in normal kidney is a prominent alteration of apoptotic regulatory molecules. The alteration of the up-regulated Fas expression might be characterized during the tumor progression stage. It is also suggested that the effect of alteration of bcl-2 expression might be minimal during the tumor progression stage because of the reduced expression in tumors of the clear cell type, which is the most dominant cell type in RCC.