Tsunoda Akira, Iijima Takeru, Tsunoda Yuko, Nakao Kentaroh, Miyaki Michiko, Kusano Mitsuo
Second Department of Surgery, School of Medicine, Showa University, Tokyo, Japan.
Anticancer Res. 2004 Jul-Aug;24(4):2471-6.
Colorectal carcinomas were studied regarding early proof of liver metastases through determination of K-ras mutations.
Seventy-seven colorectal carcinomas were investigated for the presence of point mutations in codon 12 and 13 of the K-ras gene, using single-strand conformation polymorphism (SSCP) analysis and direct sequencing.
Twenty-six carcinomas were positive for K-ras mutations, of which 21 had codon 12 and 5 had codon 13 mutations. Twenty patients with K-ras-positive tumor (20 out of 26: 77%) developed liver metastases, of which 13 had simultaneous metastases and 7 had metachronous metastases. There was a significant association between K-ras mutations and liver metastases (p=0.03). A multivariate logistic regression model demonstrated that the involvement of lymph node (p<0.01) and K-ras mutations (p=0.02) were predictive factors for liver metastases from colorectal carcinoma. Sequencing in carcinomas without liver metastases showed the base change in the first position of codon 12, whereas with liver metastases it showed significantly frequent base change in the second position of codon 12 (p<0.01).
It is suggested that the presence of K-ras mutation, especially base change in the second position of codon 12, may predict liver metastases from colorectal carcinoma.
通过检测K-ras突变来研究结直肠癌肝转移的早期证据。
采用单链构象多态性(SSCP)分析和直接测序法,对77例结直肠癌患者的K-ras基因第12和13密码子的点突变情况进行研究。
26例癌组织K-ras突变呈阳性,其中21例为第12密码子突变,5例为第13密码子突变。20例K-ras阳性肿瘤患者(26例中的20例,占77%)发生了肝转移,其中13例为同时性转移,7例为异时性转移。K-ras突变与肝转移之间存在显著相关性(p = 0.03)。多因素逻辑回归模型显示,淋巴结受累(p < 0.01)和K-ras突变(p = 0.02)是结直肠癌肝转移的预测因素。无肝转移癌组织的测序显示第12密码子第一位碱基发生改变,而有肝转移的癌组织中第12密码子第二位碱基改变明显更频繁(p < 0.01)。
提示K-ras突变的存在,尤其是第12密码子第二位碱基的改变,可能预测结直肠癌肝转移。