Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray.

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray.
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DOI:
10.1038/sj.bjc.6600922
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发表时间:
2003-05-06
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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在许多恶性肿瘤中观察到细胞周期 G1/S 转变的异常,并且似乎在转化过程中至关重要。很少有研究描述 G1/S 调节缺陷的存在及其与肾细胞癌 (RCC) 的临床相关性。因此,我们使用组织微阵列和免疫组织化学检查了 218 个 RCC 中细胞周期蛋白 D1、D3、E 和 p27 的蛋白含量。部分肿瘤的结果通过常规组织切片的蛋白质印迹和免疫组织化学染色得到证实。有趣的是,细胞周期蛋白 D1 和 p27 的蛋白含量低与常规肿瘤患者的高核级别、大肿瘤尺寸和不良预后相关。我们进一步观察到不同 RCC 亚型之间 G1/S 监管缺陷模式的显着差异。大多数常规病例和乳头状病例均表达 p27;然而,嫌色肿瘤通常缺乏 p27 染色。此外,传统RCC通常表达高细胞周期蛋白D1蛋白水平,而乳头状肾细胞则表现出高细胞周期蛋白E水平。总之,我们已经证明RCC中存在G1/S调节缺陷,并且与临床病理参数相关。 RCC 亚型之间的细胞周期调控缺陷模式也有所不同。
Aberrations in the G1/S transition of the cell cycle have been observed in many malignancies and seem to be critical in the transformation process. Few studies have delineated the presence of G1/S regulatory defects and their clinical relevance in renal cell carcinoma (RCC). Therefore, we have examined the protein contents of cyclin D1, D3, E, and p27 in 218 RCCs, using tissue microarray and immunohistochemistry. The results from a subset of tumours were confirmed by Western blotting and immunohistochemical staining of regular tissue sections. Interestingly, low protein contents of cyclin D1 and p27 were associated with high nuclear grade, large tumour size, and poor prognosis for patients with conventional tumours. We further observed substantial differences in the pattern of G1/S regulatory defects between the different RCC subtypes. The majority of both conventional and papillary cases expressed p27; however, chromophobe tumours generally lacked p27 staining. In addition, conventional RCCs often expressed high cyclin D1 protein levels, while papillary RCCs exhibited high cyclin E. In summary, we have shown that G1/S regulatory defects are present in RCC and are associated with clinico-pathological parameters. The pattern of cell cycle regulatory defects also differed between RCC subtypes.
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