Cyclin E and P27 protein content in human renal cell carcinoma: Clinical outcome and associations with cyclin D

Cyclin E and P27 protein content in human renal cell carcinoma: Clinical outcome and associations with cyclin D
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DOI:
10.1002/ijc.10763
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发表时间:
2002-12-20
影响因子:
6.4
通讯作者:
Landberg, G
Landberg, G
中科院分区:
医学1区
文献类型:
--
作者:
Hedberg, Y;Davoodi, E;Landberg, G

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在一些恶性肿瘤中已经观察到GI-S转变中的畸变,这表明细胞周期缺陷与参与转化过程的癌基因的激活和抑制基因的失活有关。人类肾细胞癌(RCC)中GI/S畸变的频率尚未完全明确。因此,我们使用Western blotting分析了79例RCC和12例相应肾皮质组织的cyclin E含量,并使用免疫组织化学分析了73例RCC中p27阳性细胞的比例。大多数肿瘤(65%)的细胞周期蛋白E水平高于相应的正常肾皮质组织。然而,当细胞周期蛋白E水平与增殖进行比较时,只有一小部分肿瘤(80例中的3例)细胞周期蛋白E水平过高。Cyclin E水平高于中位数与非整倍性(p = 0.025)、高分期(p = 0.027)、高分级(p = 0.013)和高红细胞沉降率(ESR, p = 0.005)相关。Cyclin E与Cyclin D1呈负相关(p = 0.023),与Cyclin D3呈正相关(p = 0.003)。大多数肿瘤(76%)显示p27阳性细胞的正常比例。p27阳性与肿瘤大小呈负相关(p = 0.007),尽管p27与肿瘤增殖缺乏相关性。p27低肿瘤患者生存率较差(p = 0.002)。p27与cyclin E水平无相关性。总之,结果表明细胞周期蛋白E和/或p27的蛋白表达与肿瘤行为有关。(C) 2002 Wiley-Liss, Inc。
Aberrations in the GI-S transition have been observed in several malignancies, suggesting that cell cycle defects are linked to the activation of oncogenes and inactivation of suppressor genes involved in the transformation process. The frequency of GI/S aberrations in human renal cell carcinoma (RCC) has not been fully clarified. We have therefore analyzed the cyclin E content, using Western blotting, in 79 RCC and 12 corresponding kidney cortex tissues as well as the fraction of p27-positive cells in 73 RCCs, using immunohistochemistry. Most of the tumors (65%) exhibited higher cyclin E levels than corresponding normal kidney cortex tissues. However, only a small fraction of the tumors (3 of 80) had excessive levels of cyclin E when cyclin E levels were compared with proliferation. Cyclin E levels higher than the median value were associated with aneuploicly (p = 0.025), high stage (p = 0.027), high grade (p = 0.013) and high erythrocyte sedimentation rate (ESR; p = 0.005). Cyclin E was further inversely correlated with cyclin D1 (p = 0.023) and positively correlated with cyclin D3 (p = 0.003). Most tumors (76%) demonstrated a normal fraction of p27-positive cells. There was an inverse correlation between p27 positivity and tumor size (p = 0.007), despite a lack of correlation between p27 and proliferation. Patients with p27 low tumors had a poor survival (p = 0.002). There was no correlation between p27 and cyclin E levels. In summary, the results suggest that protein expression of cyclin E and/or p27 is linked to tumor behavior. (C) 2002 Wiley-Liss, Inc.