EZH2、p16 启动子在乳腺癌亚型中的表达 及其与临床病理特征的关系

Role of EZH2 and p16 promoter in breast cancer subtypes and its relationship with clinicopathological features

摘要:

目的 探讨EZH2 与p16 启动子甲基化与乳腺癌分子分型及临床病理参数的关系。方法 81 例乳腺 癌患者根据乳腺癌分子分型标准分组，采用免疫组织化学和甲基化特异性PCR（MSP）分别检测EZH2 蛋白表 达和p16 启动子甲基化水平，并分析各组表达差异以及与临床病理的关系。结果 EZH2 表达与组织分级、临床 分期、淋巴结转移组和ER 表达有关（P <0.05）。p16 启动子甲基化与组织分级、临床分期有关（P <0.05）。在 luminal A、luminal B、人表皮生长因子受体2（HER-2）过表达、三阴型（TNBC）组中EZH2 的阳性表达率分别 为36.3%（8/22）、36%（9/25）、60%（6/10）、70.8%（17/24），差异有统计学意义（P <0.05）。p16 启动子甲基化 率分别为27.2%（6/22）、28.0%（7/25）、40%（4/10）和54.2%（13/24），差异无统计学意义（P >0.05）。EZH2 阳性表达组p16 甲基化率高于EZH2 阴性表达组，两者呈正相关（52.5% vs 21.9%，r =0.276，P =0.004）。结论 EZH2 与p16 启动子甲基化与乳腺癌的发生发展密切相关，其中EZH2 可作为乳腺癌尤其TNBC 乳腺癌预后 评估指标之一。

Abstract:

Objective To investigate the characteristics of EZH2 and p16 promoter methylation in breast cancer and their association with molecular subtypes and clinicopathological features. Methods Totally 81 cases of breast cancer were grouped according to the standard of molecular classification of breast cancer. Immunohistochemical SP and methylation specific PCR (MSP) method were performed to detect the expression of EZH2 and the methylation level of p16 promoter. Relationship between their expression and clinicopathological features was determined. Results EZH2 expression was positively correlated with histological grade, clinical stage, lymph node metastasis and ER expression (P < 0.05). P16 methylation was positively correlated with histological grade and clinical stage (P < 0.05). Positive rate of EZH2 among group of luminalA, luminalB, HER-2, and TNBC was different (P < 0.05) [36.3% (8/22), 36% (9/25), 60% (6/10) and 70.8% (17/24), respectively]. Incidence of p16 promoter methylation was 27.2% (6/22), 28.0% (7/25), 40% (4/10) and 54.2% (13/24), respectively, without any difference (P > 0.05). Methylation level of p16 promoter was increased significantly in EZH2 positive group compared with EZH2 negative group. Positive correlation was identified between p16 promotermethylation and EZH2 (52.5% vs 21.9%, r = 0.276, P = 0.004). Conclusion EZH2 and p16 methylation correlates closely with the carcinogenesis and development of breast cancer; EZH2 may be one of prognostic biomarker in breast cancer, especially in TNBC.