Sejima Takehiro, Miyagawa Ikuo
Division of Urology, Department of Surgery, Tottori University Faculty of Medicine, Yonago, Japan.
Int J Urol. 2006 Mar;13(3):257-64. doi: 10.1111/j.1442-2042.2006.01265.x.
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.
为了明确肾细胞癌(RCC)肿瘤进展过程中凋亡调节分子表达的变化,我们比较了肿瘤组织与正常组织之间的表达情况,并评估了肿瘤中该表达与病理及临床特征的关系。
采用竞争性逆转录-聚合酶链反应(RT-PCR)和免疫组织化学(IHC)方法,测定了50例RCC手术切除的肿瘤组织和正常组织中Fas和bcl-2 mRNA及蛋白的表达。
与正常组织相比,RCC中Fas和bcl-2的mRNA表达显著降低。免疫组织化学分析支持RT-PCR结果。就与病理及临床特征的关系而言,高分期或高分级肿瘤中Fas的mRNA和蛋白表达显著高于低分期或低分级肿瘤。此外,在mRNA表达量高的肿瘤病例中观察到统计学上较差的预后。在bcl-2分析中,与嫌色细胞肿瘤相比,透明细胞肿瘤中mRNA和蛋白表达显著降低。
提示与正常肾组织相比,RCC中Fas和bcl-2表达降低是凋亡调节分子的一个显著变化。Fas表达上调的变化可能在肿瘤进展阶段具有特征性。还提示在肿瘤进展阶段,bcl-2表达变化的影响可能最小,因为在RCC中最主要的细胞类型透明细胞肿瘤中其表达降低。