Alteration of apoptotic regulatory molecules expression during carcinogenesis and tumor progression of renal cell carcinoma.

Abstract

In order to characterize the alteration of apoptotic regulatory molecule expressions during carcinogenesis and tumor progression of renal cell carcinoma (RCC), we compared the expressions between tumor and normal tissues, and evaluated the relationships between expressions in tumors with pathological and clinical characteristics. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) allowed the determination of Fas, Fas ligand (FasL), and bcl-2 mRNA expressions in surgically resected tissues of 40 cases of RCC. In comparing the mRNA expression incidence between tumor and normal tissues, RT-PCR analysis demonstrated that the Fas and bcl-2 incidence in tumors was significantly lower than that in normal tissues. An IHC analysis was supportive of the RT-PCR results that higher immunoreactivity was recognized in mRNA positive cases than in negative cases. With regard to relationships with pathological and clinical characteristics, FasL mRNA expression was recognized significantly more frequently in pT3a tumors than in pT1 tumors, and also more frequently in G2 tumors than in G1 tumors. A similar result was obtained by IHC analysis. Five patients died of cancer. Four of these patients had tumors which showed positive mRNA expression and a strong immunoreactivity of FasL. It is suggested that the alteration of the down-regulated expression of Fas and bcl-2 might contribute to the carcinogenesis of RCC. It is also suggested that the alteration of up-regulated expression of FasL in tumors, which establishes the immune evasion mechanism in some malignancies, might be characterized during the tumor progression of RCC.