Netter Jeanne, Lehmann-Che Jacqueline, Lambert Jerome, Tallet Anne, Lourenco Nelson, Soliman Hany, Bertheau Philippe, Pariente Benjamin, Chirica Mircea, Pocard Marc, Allez Matthieu, De The Hugues, Gornet Jean-Marc
AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France.
AP-HP, Saint-Louis Hospital, Department of Biochemistry, 75010 Paris, France; Inserm/CNRS UMR 944/7212, 75010 Paris, France.
Bull Cancer. 2015 Feb;102(2):117-25. doi: 10.1016/j.bulcan.2014.12.010. Epub 2015 Jan 20.
Survival of metastatic colon cancer (mCC) patients has considerably improved with optimization of new drugs regimen. Inactivation of TP53 pathway by TP53 mutations is observed in nearly half of colorectal tumors. The impact of such mutations has been poorly studied in the metastatic setting.
The files of 254 mCC treated in a single institution at Saint-Louis hospital between January 1999 and April 2011 were retrospectively reviewed. Tissue samples for analysis of TP53 mutations were available for 68 patients, performed using FASAY. The prognostic value of TP53 status was evaluated by comparing progression free survival (PFS) and overall survival (OS) in the group of TP53-mutated and wild type patients.
PFS was 6.9 months and OS 21.7 months in the whole population. There was no statistical difference in TP53-mutated and wild type groups in term of PFS (HR=1.04; IC 95%=0.6-1.79) and OS (HR=0.99; IC 95%=0.53-1.55) whatever the chemotherapy regimen (oxaliplatin- or irinotecan-based). Only BRAF V600 mutation was demonstrated to be a poor prognostic factor for PFS and OS, and CEA level for OS.
Routine determination of TP53 mutations, even with a highly sensitive method, cannot be recommended to predict chemotherapy response in mCC.
随着新药方案的优化，转移性结肠癌（mCC）患者的生存率有了显著提高。在近一半的结直肠癌肿瘤中观察到TP53突变导致TP53通路失活。此类突变在转移情况下的影响研究较少。
回顾性分析了1999年1月至2011年4月在圣路易医院同一机构接受治疗的254例mCC患者的病历。68例患者有用于分析TP53突变的组织样本，采用FASAY进行检测。通过比较TP53突变型和野生型患者组的无进展生存期（PFS）和总生存期（OS），评估TP53状态的预后价值。
总体人群的PFS为6.9个月，OS为21.7个月。无论化疗方案（基于奥沙利铂或伊立替康）如何，TP53突变型和野生型组在PFS（HR = 1.04；95%CI = 0.6 - 1.79）和OS（HR = 0.99；95%CI = 0.53 - 1.55）方面均无统计学差异。仅BRAF V600突变被证明是PFS和OS的不良预后因素，而CEA水平是OS的不良预后因素。
即使采用高灵敏度方法，也不建议常规检测TP53突变来预测mCC的化疗反应。
