Medical Department III, Hospital of the University, University of Munich, Germany.
Anticancer Drugs. 2011 Oct;22(9):913-8. doi: 10.1097/CAD.0b013e3283493160.
This retrospective study investigated the clinical characteristics of patients with metastatic colorectal cancer (mCRC) depending on the KRAS status, thereby differentiating KRAS exon 2 mutations in codon 12 versus codon 13. In total, 273 patients with mCRC receiving first-line therapy were analyzed. One hundred patients were treated within the FIRE-3 trial (FOLFIRI plus cetuximab or bevacizumab), 147 patients within the AIO KRK-0104 trial (cetuximab plus CAPIRI or CAPOX), and further 26 patients received therapy outside the study. Thirty-eight tumors with KRAS mutation in codon 13, 140 tumors with mutation in codon 12, and 95 tumors with KRAS wild type as a comparison were included in this analysis. Bivariate analyses demonstrated significant differences between KRAS wild-type, codon 12-mutated, and codon 13-mutated tumors with regard to synchronous lymph node metastasis (P=0.018), organ metastasis (76.8% vs. 65.9% vs. 89.5%, P=0.009), liver metastasis (89.5% vs. 78.2% vs. 92.1%, P=0.025), lung metastasis (29.5% vs. 42.9% vs. 50%, P=0.041), liver-only metastasis (48.4% vs. 28.8% vs. 28.9%, P=0.006), and metastases in two or more organs (49.5, 61.4, 71.1, P=0.047). Regression models indicated a significant impact of KRAS mutations in codon 12 versus codon 13 for synchronous organ and nodal metastasis (P=0.01, 0.03). This pooled analysis indicates that mCRC is a heterogeneous disease, which seems to be defined by KRAS mutations of the tumor. Compared with KRAS codon 12 mutations, codon 13-mutated mCRC presents as a more aggressive disease frequently associated with local and distant metastases at first diagnosis.
本回顾性研究根据 KRAS 状态调查了转移性结直肠癌（mCRC）患者的临床特征，从而区分了密码子 12 与密码子 13 中的 KRAS 外显子 2 突变。共分析了 273 例接受一线治疗的 mCRC 患者。其中 100 例接受 FIRE-3 试验（FOLFIRI 加西妥昔单抗或贝伐单抗）治疗，147 例接受 AIO KRK-0104 试验（西妥昔单抗加 CAPIRI 或 CAPOX）治疗，另有 26 例在研究之外接受治疗。本分析纳入了 38 例 KRAS 密码子 13 突变肿瘤、140 例密码子 12 突变肿瘤和 95 例 KRAS 野生型肿瘤作为对照。双变量分析显示，KRAS 野生型、密码子 12 突变型和密码子 13 突变型肿瘤之间在同步淋巴结转移（P=0.018）、器官转移（76.8% vs. 65.9% vs. 89.5%，P=0.009）、肝转移（89.5% vs. 78.2% vs. 92.1%，P=0.025）、肺转移（29.5% vs. 42.9% vs. 50%，P=0.041）、仅肝转移（48.4% vs. 28.8% vs. 28.9%，P=0.006）和两个或更多器官转移（49.5%、61.4%、71.1%，P=0.047）方面存在显著差异。回归模型表明，KRAS 密码子 12 与密码子 13 突变对同步器官和淋巴结转移具有显著影响（P=0.01，0.03）。这项汇总分析表明，mCRC 是一种异质性疾病，似乎由肿瘤的 KRAS 突变定义。与 KRAS 密码子 12 突变相比，密码子 13 突变的 mCRC 表现为一种侵袭性更强的疾病，在初次诊断时常常与局部和远处转移相关。
