p53变异在结肠癌原发灶和肝转移灶的配对比较及其与术后生存的关系

The composition of p53 status between primary and liver metastatic colorectal cancer, and its relationship with survival after hepatectomy

目的 :了解 p5 3基因及其蛋白在大肠癌发生、转移过程中的动态变化以及p5 3变异与生存期的关系。方法 :以DenaturingGradientGelElectrophoresis (DGGE)及自动DNA序列分析检测p5 3基因exon 5～ 9。 结果 :41例被检病人中 2 6例呈p5 3变异 (6 3% ) ,其中 6例仅在肝转移灶发现 p5 3变异 ,其余均为原发灶、转移灶一致性的变异。另有 3例原发灶已有 p5 3变异的病人 ,在转移灶出现了新增加的变异。生存分析显示 ,在肝转移灶含变异型 p5 3的病人比含野生型 p5 3者具有更长的术后生存期。 结论 :大肠癌肝转移 ,p5 3变异主要开始于肠癌原发灶 ,并保持于转移至肝脏的癌细胞内 ,小部分p5 3变异也可以始发于转移灶。实施肝部分切除术的患者 ,转移癌灶含变异型 p5 3者的术后生存期比含野生型p5 3者长。

Objective:To investigate p53 gene status during the processes of the occurrence of colorectal carcinoma and metastasis,and the relationship between p53 mutation and survival Methods:p53 gene status (exon5～9) was examined by PCR, Denaturing Gradient Gel Electrophoresis (DGGE) and automated sequencing Results:p53 alterations were found in exons 5 through 9 at 26 of 41 patients (63%) Among them, 6 patients had mutations only in the liver metastatic lesions but not in their original tumors, while the others were found the same mutation on both of primary colorectal and hepatic metastatic lesions, and an additional mutation in the metastatic lesions was found in three cases Surviving analysis revealed that, after hepatectomy the patients with p53 mutations had a longer survival than those with wild p53 Conclusion:p53 mutations, for the colorectal carcinomas followed by hepatic metastases, mainly start in the primary colorectal lesion and then is kept and brought into hepatic organ; it also might start from metastatic lesion in a few cases For the patients who had colorectal cancer liver metastasis and underwent partial hepatectomy, the survival time is longer in mutant p53 group than in wild type p53 group