Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer
Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer
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DOI：
10.1158/1078-0432.ccr-03-0751
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发表时间：
2004-08-01
影响因子：
11.5
通讯作者：
Henshall, SM
中科院分区：
文献类型：
--
作者：
Bali, A;O'Brien, PM;Henshall, SM
目的：细胞周期控制的失调，尤其是G（1）-S期转变，与大多数人类癌症的发病机理有关，包括上皮卵巢癌（EOC）。然而，EOC中异常细胞周期基因表达的预后意义仍然不清楚。经验性设计：调节G（1）-s相进展的PRB途径中所选基因的表达E，P27（KIP1），P21（WAF1/CIP1）和p53在连续的134系列中检查serous EOC using immunohistochemistry and the results correlated to disease outcome.Results: Molecular markers predictive of reduced overall survival in univariate analysis were overexpression of cyclin D1 (P = 0.03) and p53 (P = 0.03) and reduced expression of p27(Kip1) ( p = 0.05）和p21（waf1/cip1）（p = 0.02），与后三个也是较短的无进展间隔的预后。此外，表现出p53过表达的患者同时丧失了p21（WAF1/CIP1）的总体较短（p = 0.0008）和无进展生存率（p = 0.0001）。在多变量分析中，在p53过表达的情况下，细胞周期蛋白D1的过表达和p21的综合损失（WAF1/CIP1）是整体存活的独立预测指标。同样，p21（WAF1/CIP1）损耗和p53过表达的组合独立地预测了较短的无进展间隔。 p53和细胞周期蛋白E的过表达以及p27（KIP1）和p21（WAF1/CIP1）的表达降低与肿瘤成绩的升高显着相关。结论：这项研究证实，细胞周期基因的失调在EOC中很常见，并且在EOC中很常见关键细胞周期调节蛋白可以预测浆液EOC中的患者预后。
Purpose: Dysregulation of cell cycle control, in particular G(1)-S-phase transition, is implicated in the pathogenesis of most human cancers, including epithelial ovarian cancer (EOC). However, the prognostic significance of aberrant cell cycle gene expression in EOC remains unclear.Experimental Design: The expression of selected genes from the pRb pathway that regulates G(1)-S-phase progression, including cyclin D1, p16(Ink4a), cyclin E, p27(kip1), p21(Waf1/Cip1), and p53, was examined in a consecutive series of 134 serous EOC using immunohistochemistry and the results correlated to disease outcome.Results: Molecular markers predictive of reduced overall survival in univariate analysis were overexpression of cyclin D1 (P = 0.03) and p53 (P = 0.03) and reduced expression of p27(Kip1) (P = 0.05) and p21(Waf1/Cip1) (P = 0.02), with the latter three also being prognostic for a shorter progression-free interval. In addition, patients displaying overexpression of p53 with concurrent loss of p21(Waf1/Cip1) had a significantly shorter overall (P = 0.0008) and progression-free survival (P = 0.0001). On multivariate analysis, overexpression of cyclin D1 and combined loss of p21(Waf1/Cip1), in the presence of p53 overexpression were independent predictors of overall survival. Similarly, the combination of p21(Waf1/Cip1) loss and p53 overexpression was independently predictive of a shorter progression-free interval. Overexpression of p53 and cyclin E and reduced expression of p27(Kip1) and p21(Waf1/Cip1) were significantly associated with increasing tumor grade.Conclusions: This study confirms that dysregulation of cell cycle genes is common in EOC, and that aberrant expression of critical cell cycle regulatory proteins can predict patient outcome in serous EOC.