BACKGROUND:Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. METHODS:Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. RESULTS:Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. CONCLUSIONS:ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance.

译文

背景:认识到对当前标准顺铂和紫杉醇治疗的耐药性或易感性可以改善转移性或复发性宫颈癌的治疗效果。
方法:从参与顺铂和异环磷酰胺II期试验(有或没有紫杉醇)的患者中收集45份组织样本进行逆行分析。进行免疫组织化学和基因分型以测试ERCC1,IIIβ-微管蛋白,COX-2,CD4,CD8和ERCC1(C8092A和N118 N)和MDR1(C3435T和G2677T)基因多态性,作为可能的预测和预后标志物。对结果进行统计分析,并与患者特征和结局相关联。
结果:ERCC1表达水平较高的患者的PFS和OS短于ERCC1表达水平较低的患者(mPFS:5.1 vs 10.2个月,p = 0.027; mOS:10.5 vs. 21.4个月,p = 0.006)。 ERCC1 N118 N位点为TT的患者,MDR1 G2677 T位点为GT的患者的PFS明显更长(分别为p = 0.006和p = 0.027)。 ERCC1表达和ERCC1 N118 N多态性仍然是PFS的独立预测因子。有趣的是,与较低的IIIβ-微管蛋白表达[15/23(65.2%)]相比,较高的IIIβ-微管蛋白表达与化疗耐药性相关且反应较少[5/20(25%)](p = 0.008)。最后,IIβ-微管蛋白水平和化疗方案是对治疗反应的独立预测因子。
结论:ERCC1表达被证明是我们基于顺铂化疗的转移性或复发性宫颈癌患者生存的重要预后因素。 ERCC1 N118 N和MDR1 G2677 T多态性也证明对疾病进展具有预后意义,而IIIβ-微管蛋白的过表达与化疗耐药性呈正相关。

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