MDR1 and ERCC1 Expression Predict Outcome of Patients with Locally Advanced Bladder Cancer Receiving Adjuvant Chemotherapy
MDR1 and ERCC1 Expression Predict Outcome of Patients with Locally Advanced Bladder Cancer Receiving Adjuvant Chemotherapy
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DOI：
10.1593/neo.10402
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发表时间：
2010-08-01
期刊：
影响因子：
4.8
通讯作者：
Hartmann, Arndt
中科院分区：
文献类型：
--
作者：
Hoffmann, Andreas-Claudius;Wild, Peter;Hartmann, Arndt
目的：辅助化疗在局部晚期膀胱癌患者中的作用仍有待确定。我们假设评估化疗反应调节剂多药耐药基因 1 (MDR1) 和切除修复交叉互补基因 1 (ERCC1) 的基因表达可能有助于确定受益于顺铂辅助化疗的患者组。实验设计：本研究纳入了来自 108 名局部晚期膀胱癌患者的福尔马林固定石蜡包埋的肿瘤样本，这些患者已入组 AUO-AB05/95，这是一项 3 期试验，随机最多三个疗程的辅助顺铂和甲氨蝶呤 (CM) 与甲氨蝶呤、长春碱、表柔比星和顺铂 (M-VEC)。通过激光捕获显微切割回收肿瘤细胞，并使用定量实时逆转录聚合酶链反应测定分析 MDR1 和 ERCC1 表达。通过多变量 Cox 比例风险回归分析将基因表达水平与临床结果相关联。结果：MDR1 和 ERCC1 的表达与总体无进展生存期独立相关（分别为 P = .001，相对风险 = 2.9 和 P = .01，相对风险 = 2.24）。在接受 M-VEC 的患者中，高 MDR1 表达与较差结果的相关性更强，而 ERCC1 分析在 CM 和 M-VEC 组中表现相同。结论：MDR1 和 ERCC1 基因高表达与局部晚期膀胱癌顺铂辅助化疗后较差的预后相关。有必要进行前瞻性研究来明确 MDR1 和 ERCC1 分析在局部晚期膀胱癌个体化多模式治疗中的作用。肿瘤 (2010) 12, 628-636
PURPOSE: The role of adjuvant chemotherapy in patients with locally advanced bladder cancer still remains to be defined. We hypothesized that assessing the gene expression of the chemotherapy response modifiers multidrug resistance gene 1 (MDR1) and excision repair cross-complementing 1 (ERCC1) may help identify the group of patients benefiting from cisplatin-based adjuvant chemotherapy. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 108 patients with locally advanced bladder cancer, who had been enrolled inAUO-AB05/95, a phase 3 trial randomizing a maximum of three courses of adjuvant cisplatin and methotrexate (CM) versus methotrexate, vinblastine, epirubicin, and cisplatin (M-VEC), were included in the study. Tumor cells were retrieved by laser-captured microdissection and analyzed for MDR1 and ERCC1 expression using a quantitative real-time reverse transcription-polymerase chain reaction assay. Gene expression levels were correlated with clinical outcomes by multivariate Cox proportional hazards regression analysis. RESULTS: Expressions of MDR1 and ERCC1 were independently associated with overall progression-free survival (P = .001, relative risk = 2.9 and P = .01, relative risk = 2.24, respectively). The correlation of high MDR1 expression with inferior outcome was stronger in patients receiving M-VEC, whereas ERCC1 analysis performed equally in the CM and M-VEC groups. CONCLUSIONS: High MDR1 and ERCC1 gene expressions are associated with inferior outcome after cisplatin-based adjuvant chemotherapy for locally advanced bladder cancer. Prospective studies are warranted to define a role for MDR1 and ERCC1 analysis in individualizing multimodality treatment in locally advanced bladder cancer. Neoplasia (2010) 12, 628-636