Alteration of cell cycle regulators correlates with survival in epithelial ovarian cancer patients
Alteration of cell cycle regulators correlates with survival in epithelial ovarian cancer patients
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DOI：
10.1016/j.humpath.2003.07.018
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发表时间：
2004-02-01
期刊：
影响因子：
3.3
通讯作者：
Kawamura, N
中科院分区：
文献类型：
--
作者：
Hashiguchi, Y;Tsuda, H;Kawamura, N
p16-cyclinD1/CDK4-pRb途径（RB途径）和p 4ARF-MDM2-p53途径（p53途径）在G1-S检查点工作，ATM-chk2-CDC25-cyclinB1/cdk1途径在G2-M检查点工作。这些途径的破坏被认为与人类癌症的预后有关。在本研究中，我们通过免疫组织化学分析了 107 例上皮性卵巢癌 (EOC) 患者中这些通路的状态，并评估了这些结果与化疗反应和预后的关系。分别在 50.5% (54/107)、51.4% (55/107) 和 33.6% (36/107) 的病例中检测到改变的 RB、p53 和 G2 通路。 RB 通路正常的患者的总生存率 (OS) 为 77.3%，显着高于 R 3 通路改变的患者的 50.0% 的 OS（通过 Kaplan-Meier 分析，P=0.0021）。 G2 通路正常患者的 OS 为 66.2%，显着高于 G2 通路改变患者的 OS 58.3% (P=0.0416)。然而，p53 通路的状态与 OS 无关。通过单变量和多变量分析，晚期、高组织学分级、RB 途径改变和 G2 途径改变是 OS 不良的重要预测因素。然而，通路状态和化疗反应之间没有显着关系。 RB通路和G2通路的状态是EOC的独立预后因素。
The p16-cyclinD1/CDK4-pRb pathway (RB pathway) and p 4ARF-MDM2-p53 pathway (p53 pathway) work at the G1-S checkpoint, and the ATM-chk2-CDC25-cyclinB1/cdk1 pathway works at the G2-M checkpoint. The disruption of these pathways is thought to be related to the prognosis of human cancer. In this study, we analyzed the status of these pathways in 107 epithelial ovarian cancer (EOC) patients by immunohistochemistry and evaluated the relationship of these results with chemotherapy response and the prognosis. Altered RB, p53, and G2 pathways were detected in 50.5% (54/107), 51.4% (55/107), and 33.6% (36/107) of cases, respectively. The overall survival (OS) of 77.3% for patients with a normal RB pathway was significantly higher than the OS of 50.0% for patients with an altered R 3 pathway (by Kaplan-Meier analysis, P=0.0021). The OS of 66.2% for patients with a normal G2 pathway was significantly higher than the OS of 58.3% for patients with an altered G2 pathway (P=0.0416). However, the status of the p53 pathway was not related to OS. By univariate and multivariate analyses, advanced stage, high histological grade, altered RB pathway, and altered G2 pathway were significant predictors of poor OS. However, there was no significant relationship between pathway status and chemotherapy response. The status of the RB pathway and of the G2 pathway were independent prognostic factors of EOC.