结直肠癌组织中PIK3CA基因突变与AKT1/2蛋白的表达及其意义

Mutation of PIK3CA Gene and Expression of AKT1/2 in Human Colorectal Cancer and their Biological Significance

目的探讨结直肠癌患者PIK3CA基因第9、20外显子点突变率及其与AKT1/2蛋白表达的关系。方法用免疫组织化学EnVision法和SSCP-PCR(单链构象多态性聚合酶链反应)分别检测42例结直肠癌组织AKT1/2蛋白表达情况和PIK3CA基因第9、20外显子突变情况,并与20例健康体检者正常大肠黏膜作对照。结果AKT1/2蛋白在PIK3CA基因突变组中比无突变对照组有更高表达(P<0.05);AKT1/2蛋白在结直肠癌组织中表达显著高于正常结直肠黏膜(P<0.05);AKT1/2蛋白表达与有无淋巴结转移、癌组织浸润程度、临床分期有关(P<0.05);14.3%(6/42)的结直肠癌存在PIK3CA基因突变;PIK3CA基因在结直肠癌组织中突变率明显高于癌旁正常黏膜(P<0.05)。PIK3CA基因突变与AKT1/2蛋白阳性表达低度相关。结论PIK3CA基因在结直肠癌中存在高频率突变,该基因的突变导致AKT1/2蛋白表达上调,可能在结直肠癌进展过程中起重要作用。

Objective To study the point mutation of PIK3CA gene of exon 9 and 20 and it＇s relationship with protein expression of AKT1/2 in human colorectal cancer.Methods SSCP-PCR was performed to detect the mutations of the 9th and 20th exon of PIK3CA in 42 cases of human colorectal cancer,and the AKT1/2 protein expression were determined by the En Vision two-step immunohistochemical method in 42 cases of healthy human.Results AKT1/2 protein expression was significantly higher in PIK3CA gene mutation tissue than that in non-mutation tissue（P〈0.05）;The positive expression rate of AKT1/2 in colorectal cancer was markedly higher than that of chronic mucosal inflammation（P〈0.05）;AKT1/2 expression were related to lymph node metastasis,tumor infiltration and clinical stage（P〈0.05）;PIK3CA gene mutation existed in 14.3%（6/42）of colorectal cancer;the mutation rate of PIK3CA gene was markedly higher in the tumor tissue than that in the adjacent normal tissue（P〈0.05）;PIK3CA gene mutation was low correlate to the AKT1/2 expression.Conclusion Mutations frequency of PIK3CA gene in human colorectal cancers is high,and the mutation upregulate the AKT1/2 expression,which may play a role in the pathogenesis of human colorectal cancer.