乳腺癌组织p16基因甲基化与ER、PR、HER2及p53表达的关系

Correlation between p16 gene methylation and expression of ER,PR,HER2 and p53 in breast cancer

目的探讨乳腺癌组织中p16基因甲基化与相关受体表达的相关性,进一步提高乳腺癌的诊断水平。方法采用甲基化特异性PCR(MSP)法检测86份乳腺癌组织及40份乳腺癌患者血清中p16基因的甲基化状态;采用免疫组化SP法检测乳腺癌组织中雌激素受体(ER)和孕激素受体(PR)、人类表皮生长因子受体2(HER2)及p53基因表达,分析各指标之间及与乳腺癌之间的关系。结果乳腺癌组织及血清中p16基因甲基化率分别为29.1%、27.5%;15例ER、PR、HER2均为阴性表达者(三阴乳腺癌),p16基因甲基化率为86.67%(13/16),非三阴乳腺癌71例,p16基因甲基化率为16.9%(12/71),P<0.01。p16基因甲基化与ER、PR蛋白表达呈负相关(r=-0.425、-0.512,P均<0.05),与HER2表达呈正相关(r=0.443,P<0.05);与p53表达无明显相关性。结论 p16基因甲基化是乳腺癌中常见的分子改变,其与ER、PR、HER2联合检测可作为乳腺癌早期诊治及预后判断的重要指标。

Objective To investigate the correlationship between pl6 gene methylation and expression of related receptom in breast cancer, and thus to further improve the diagnosis of breast cancer. Methods Methylation-specific PCR （MSP） were used to detect the methylation status of pl6 gene in 86 breast cancer tissues and serum of 40 patients; the expression of estrogen receptor（ ER）, progesterone receptor（PR） , human epidermal growth factor receptor 2 （ HER2 ） and p53 in those specimens were examined by immunohistochemistry. Spearman was used to study the correlations between them. Resuits The methylation frequencies of pl6 were 29.1% in breast cancer tissues and 27.5% in serum of patients. There was concordance between pl6 methylation in cancer tissues and serum. The methylation frequencies of pl6 were 86.67% （ 13/ 16） in 15 triple-negative cancers and 16.90% （12/71）in 71 none triple-negative cancers ,P 〈0.01. p16 hypermethylation was negatively associated with ER and PR expression （ r = - 0. 425, - 0.512, both P 〈 0.05 ） and positively associated with HER2（r =0. 443 ,P 〈 0.05 ）. No significant correlation was found between pl6 methylation and p53 expression. Conclusions pl6 gene methylation is a common molecular alteration in breast cancer,joint detection of p16 methylation and expression of ER,PR, HER2 and p53 can be used as potential indicators in early diagnosis ,treament and prognosis of breast cancer.