MDM2-P53反馈调节对大肠癌作用的临床病理学研究

A clinicopathological study of the Relationship of MDM2 and P53 gene with biological behavior in colorectal carcinoma

目的分析MDM2基因扩增、P53基因缺失与蛋白异常表达在大肠癌发生演进中的作用、与临床病理因素的关系。方法应用RT-PCR、FISH和免疫组化技术,检测72例大肠癌组织MDM2基因扩增、p53基因缺失以及其蛋白表达特点。结果大肠癌MDM2基因扩增、p53基因缺失率为28.1%和53.1%,两蛋白表达阳性率为43.0%和65.0%。MDM2、p53蛋白在肝转移、淋巴结转移组中表达明显增多,与对照组比较差异有显著性(P=0.011);p53基因缺失、MDM2基因扩增在有静脉侵袭大肠癌组明显高于无静脉侵袭组(60.7%和31.8%),MDM2蛋白表达与癌细胞对静脉侵袭性有关(P=0.016)。结论 MDM2、p53基因参与大肠癌发生发展过程,MDM2在肝转移组、静脉侵袭组表达明显增多,可作为肝内微小转移的参考指标,MDM2、p53蛋白表达与淋巴结转移、肝转移有明显相关性,提示预后不良,两基因联合检测对大肠癌预后评估有重要意义。

Objective To investigate the relationship of MDM2 gene,P53 gene with clinicopathologic parameters in colorectal carcinoma.Methods The detection of MDM2 amplification,p53 deletion and their protein in 72 patients by RT-PCR,FISH and immunohistochemical technique.Results The ratio of MDM2 and P53 gene expression in the group of the colorectal carcinoma was 28.1% and 53.1%,but protein expression was 43.0% and 65.0%,respectively.Expression of MDM2 and p53 protein was higher in the groups of lymph node metastasis than nometastasis,their difference had significant in statistics（P=0.011）;expression of MDM2 between the groups of venous invasion（60.7%） and noinvasion（31.8%） was also shown evidently difference（P=0.016）.Conclusions MDM2-P53 pathway is a part of the carcinogensis of the colorectal carcinoma.The relationships of the expression of MDM2 gene and p53 gene were significantly detected with the liver metastasis,with lymph node metastasis and with venous invasion in colorectal carcinoma.MDM2 gene amplification was demonstrated and associated the relationship with venous invasion and liver metastasis significantly.This study suggests that the expression of MDM2 and p53 gene seem to be greater value as a biomarker of liver metastasis,lymph node metastasis and venous invasion in colorectal carcinoma.