Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria.
Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Clinical Biometrics, Medical University of Vienna, 1090 Vienna, Austria.
EBioMedicine. 2015 Jun 8;2(8):825-30. doi: 10.1016/j.ebiom.2015.06.003. eCollection 2015 Aug.
We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344-3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.
我们假设辅助 5-氟尿嘧啶（5FU）在 III 期结肠癌中的治疗效果不同与 TP53 突变状态有关。ABCSG-90 是一项前瞻性随机试验，研究了辅助 5FU 在 III 期结肠癌患者中的作用。这些患者中有 70%（389/572）的肿瘤材料可用于使用 TP53 基因特异性 Sanger 测序方案分析生物标志物 TP53。中位随访时间为 88 个月。TP53 突变频率为 33%。发现 TP53 状态、结果和淋巴结分类之间存在显著的相互作用（P=0.0095）。在 N1 分类中，TP53 野生型患者的总生存明显优于 TP53 突变型（5 年总生存率分别为 81.0%和 62.0%；HR=2.131；95%CI：1.344-3.378；P=0.0010）。在 N2 分类中，TP53 状态对生存没有影响（P=0.4992）。在 TP53 野生型患者中，淋巴结分类的预后意义显著增强（P=0.0002）。在 TP53 突变型患者中，N1 和 N2 患者的生存曲线重叠，淋巴结分类不再具有预后意义。生物标志物 TP53 独立预测了辅助 5FU 在 N1 结肠癌患者中的疗效。TP53 在 N2 患者中没有预测作用，5FU 在这些患者中已知没有作用。
