Expression of cyclin E and the cyclin-dependent kinase inhibitor p27 in malignant lymphomas-prognostic implications.
Expression of cyclin E and the cyclin-dependent kinase inhibitor p27 in malignant lymphomas-prognostic implications.
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恶性淋巴瘤中细胞周期蛋白 E 和细胞周期蛋白依赖性激酶抑制剂 p27 的表达 - 预后意义。
作者：
M. Erlanson;Cajsa Portin;B. Linderholm;J. Lindh;G. Roos;G. Landberg
细胞周期蛋白E和细胞周期蛋白依赖性激酶抑制因子p27是G1-S转变过程中调控细胞周期蛋白依赖性激酶活性的两个重要调节因子。细胞周期控制的异常经常在肿瘤中被观察到，甚至在肿瘤的发展中可能是强制性的。为了探讨细胞周期缺陷在恶性淋巴瘤中的重要性，我们用免疫组织化学方法研究了105例新诊断的淋巴瘤中细胞周期蛋白E和p27的表达。P27和细胞周期蛋白E的表达呈显著负相关(r_s=-0.24，P=0.02)，两者与S期细胞比例呈正相关(r_s=-0.35，P&t；.001和r_s=)。45，P<；.001)。在一些淋巴瘤中，p27的表达和增殖之间的负相关被取消，这表明p27的下调可以代表真正的异常。对105例患者进行生存分析，中位观察时间为86个月。P27低表达和细胞周期蛋白E高表达与预后不良显著相关(P=0.05)。0001和.03)。在多因素COX分析中，p27表达、分期、血清乳酸脱氢酶水平、分级和年龄是独立的预后因素，而S分期和细胞周期蛋白E的表达是独立的预后因素。这是首次报道p27在恶性淋巴瘤中的表达具有独立的预后意义，这需要进一步研究其在淋巴系统肿瘤发生中的生物学作用。
Cyclin E and the cyclin-dependent kinase inhibitor p27 are two important regulators of the G1-S transition modulating the activity of cyclin-dependent kinases. Aberrations in the cell cycle control are often observed in tumors and might even be mandatory in tumor development. To investigate the importance of cell-cycle defects in malignant lymphomas we have characterized the expression of cyclin E and p27 in 105 newly diagnosed lymphomas using immunohistochemistry. A significant, inverse correlation between p27 and cyclin E expression was observed (rs = -.24, P = .02) and both proteins correlated with the S-phase fraction (rs = -.35, P < .001 and rs = . 45, P < .001, respectively). The inverse relationship between p27 expression and proliferation was abrogated in some lymphomas, suggesting that p27 downregulation can represent a genuine aberration. Survival analysis was performed in 105 patients with a median observation time of 86 months. Low p27 and high cyclin E expression were significantly associated with a poor prognosis (P = . 0001 and .03, respectively). In a multivariate Cox analysis, p27 expression, stage, serum lactate dehydrogenase level, grade, and age were independent prognostic factors, in contrast to S-phase fraction and cyclin E expression. This is the first report showing that p27 expression in malignant lymphomas has independent prognostic significance, which necessitates future studies regarding its more precise biological role in lymphoid tumorogenesis.
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