直肠癌患者中K-ras基因12位点突变及p21蛋白表达的研究

The mutation of the K - ras 12th codon and the expression of p21 in rectal cancer

目的 检测K-ras基因12位点突变和p21蛋白表达在直肠癌中的作用,并探讨K-ras基因12位点突变、p21蛋白表达与临床、病理参数之间的关系.方法 收集52例直肠癌手术标本,应用常规方法提取直肠癌组织和相应癌周正常组织的DNA、聚合酶链反应（PCR）扩增、单链构象多态性（SSCP）电泳,检测K-ras基因12位点的突变情况,用免疫组织化学方法检测p21蛋白的表达.结果 直肠癌发生K-ras基因12位点突变为44.2%,相应癌周正常组织中未检出K-ras基因12位点突变,差异有统计学意义（P＜0.01）.p21蛋白表达率为63.46%,明显高于相应癌周正常组织的表达率,差异有统计学意义（P＜0.01）.K-ras基因突变与性别、年龄、肿瘤大小、肿瘤浸润深度、组织学类型、淋巴结转移、远处转移无关.p21蛋白高表达与淋巴结转移密切相关（P＜0.01）,与远处转移有关（P＜0.05）,与患者性别、年龄、肿瘤大小、肿瘤浸润深度、组织学类型无关（P＞0.05）.结论 K-ras基因12位点的突变是直肠癌发生的重要事件,可作为一种诊断标志物.p21蛋白表达与直肠癌发生密切相关,可作为一种免疫标志物,并可用于判断直肠癌的预后.

Objective To examine the mutation of the K- ras 12th codon and p21 expression in the pathogenesis of rectal cancer,and the relations among the K -ras codon 12 mutation, the p21 expression and the clinicopathological parameters. Methods A total of 52 samples of rectal cancer were detected for the mutation of the K -ras 12th codon and the p21 expression by PCR, SSCP and immunochemistry respectively. The relations among the K - ras codon 12 mutation, the p21 expression and the clinicopathological parameters were analyzed. Results The rate of the K - ras codon 12 mutation was 44.2 % , but no such mutation was found in the adjacent normal tissue （ P 〈 0.01 ）. The rate of p21 expression was 63.46%, which was much higher than that in the normal tissue （ 3.85 % ） （ P 〈 0. 01 ）. The K - ras codon 12 mutation was not related to the gender, age, tumor size, infiltration, histological type, lymph node metastasis, distant metastasis （P 〉 0.05 ）. The expression of p21 was related to lymph node metastasis （ P 〈 0.01 ） and distant metastasis （ P 〈 0.05 ） but not to gender,age, tumor size, infiltration and histological type （ P 〉 0.05 ）. Conclusion The mutation of the K - ras 12th codon may be the early event in the development of rectal cancer, and can be used as a diagnostic marker. As the p21 expression correlates closely to the morbidity of rectal cancer,it may be used as an immunohistochemical marker for estimating the prognosis of rectal cancer.