三阴性乳腺癌中PTEN基因启动子甲基化的临床意义

Clinical significance of PTEN gene promoter methylation in triplenegative breast cancer

目的：检测三阴性乳腺癌组织中第10号染色体缺失的磷酸酶和张力蛋白同源基因（phosphatase and tensin homology deleted on chromosome ten,PTEN）启动子区的甲基化情况,并分析其与患者临床病理特征的相关性。方法：选取60例三阴性乳腺癌组织标本和16例正常乳腺组织标本（作为对照组）,采用焦磷酸测序法检测各组织中PTEN基因启动子区的甲基化率,并采用免疫组织化学法测定Ki-67、E-钙黏蛋白（E-cadherin）、血管内皮生长因子（vascular endothelial growth factor,VEGF）、p53和表皮生长因子受体（epidermal growth factor receptor,EGFR）蛋白的表达,然后统计分析PTEN基因甲基化率与三阴性乳腺癌患者不同临床及病理学特征之间的关系。结果：三阴性乳腺癌组织中PTEN基因启动子区甲基化率明显高于正常乳腺组织（P〈0.05）。三阴性乳腺癌患者中,临床Ⅲ期的PTEN基因启动子区甲基化率明显高于0~Ⅱ期（P〈0.01）,有淋巴结转移者高于无淋巴结转移者（P〈0.01）,VEGF和p53蛋白中高表达组高于不表达和低表达组（P值均〈0.01）,Ki-67≥14%组高于Ki-67〈14%组（P〈0.01）。结论：PTEN基因启动子区甲基化可能与三阴性乳腺癌的临床分期、淋巴结转移以及VEGF、p53和Ki-67表达水平具有相关性,提示其可能在三阴性乳腺癌的发生和发展中起重要作用。

Objective： To detect the methylation status of phosphatase and tensin homology deleted on chromosome ten （PTEN） gene promoter in triple-negative breast cancer, and to analyze the correlation of PTEN gene methylation with the clinical and pathological characteristics of breast cancer patients.Methods： All of sixty cases of triple-negative breast cancer tissue specimens and sixteen cases of fresh normal breast tissue specimens （as the control） were selected. The methylation rate of PTEN gene promoter in the two groups was detected by pyrophosphate sequencing method. The expression levels of Ki-67, E-cadherin, vascular endothelial growth factor （VEGF）, p53, and epidermal growth factor receptor （EGFR） were determined by immunohistochemical method. Then the relationships of PTEN gene rnethylation rate and the different clinical and pathological parameters of patients with triple-negative breast cancer were statistically analyzed.Result： The methylation rate of PTEN gene promoter in triple-negative breast cancer tissues was significantly higher than that in normal breast tissues （P 〈 0.05）. For the patients with triple-negative breast cancer, the methylation rate of PTEN gene in cancer tissues at stage Ⅲ was higher than that at stage 0-Ⅱ （P 〈 0.01）, the one with lymph node metastasis was higher than that without lymph node metastasis （P 〈 0.01）. Moreover, the methylation rates of PTEN gene in triple-negative breast cancer tissues with medium and high expressions of VEGF and p53 were higher than those with negative and low expressions of VEGF and p53 （both P 〈 0.01）, and the one with Ki-67 level ≥ 14 % was higher than that with Ki-67 〈 14 % （P 〈 0.01）.Conclusion： The methylation status of PTEN gene promoter in triple-negative breast cancer tissues may be related with the clinical stage, lymph node metastasis and the expressions of VEGF, p53 and Ki-67 proteins, suggesting that PTEN gene methylation may play an important role in the occurrence and development of triple-negative breast cancer.