乳腺癌中p53基因DNA水平突变与核蛋白水平突变的比较

Comparison of nuclear accumulation of p53 protein with mutations in the p53 gene on the tissues of human breast cancer

目的研究ｐ５３基因ＤＮＡ水平和蛋白水平的突变。方法分别采用多聚酶链反应单链构象多态分析银染方法和链酶亲和素生物素过氧化物酶复合物（ｓｔｒｅｐａｖｉｄｉｎｂｉｏｔｉｎｐｅｒｏｘｉｄａｓｅｃｏｍｐｌｅｘ，ＳＡＢＣ）免疫组化方法，检测了５４例乳腺浸润性导管癌标本。结果２２例在ＤＮＡ水平突变阳性，突变率为４１％；３２例在核蛋白水平突变，突变率５７％。其中２２例ＤＮＡ突变阳性者，核蛋白突变均阳性；而３２例ＤＮＡ水平突变阴性者，核蛋白突变阳性者９例，占２８％。ｐ５３ＤＮＡ突变与核蛋白突变之间有显著相关性，并且两者都与患者的淋巴结转移以及雌、孕激素受体表达有关（Ｐ＜００１）。结论免疫组化是一种快速检测ｐ５３是否存在异常的有效方法。但是在蛋白水平突变阳性者中存在一定的假阳性。

Objective To compare nuclear accumulation of p53 protein with mutations in the p53 gene on the tissues of human breast cancer. Method Fifty four invasive ductal carcinomas of breast were analyzed by polymerase chain reaction single strand conformational polymorphism(PCR SSCP) silver stain and strep avidin biotin peroxidase complex (SABC) immunohistochemistry. Result A highly significant association between the presence of p53 gene mutation and nuclear accumulation of p53 protein was found( r =0 714, P <0 01). All 22 tumors with p53 gene mutations showed nuclear accumulation of p53 protein. Of the 32 tumors with gene mutations undetected, 9(28%) showed nuclear accumulation of p53 protein.Both p53 mutation protein and p53 gene mutations were prevalent in steroid and progesterone receptors negative tumors( P <0 05). There was a statistically significant association between the nuclear accumulation of p53 protein and lymphonode invasion ( P <0 05). So did p53 gene mutations ( P <0 05). Therefore, p53 abnormalities might be associated with an aggressive phenotype in breast cancer. Conclution The immunohistochemical detection of nuclear p53 protein accumulation is highly associated with p53 gene mutations in breast cancer tissues. This method is useful for rapid screening of p53 abnormalities. In some cases of slightly positive for p53 nuclear protein we must observe p53 genemutations to avoid the false positive reaction.