摘要
目的检测RUNX3在腺腔A(luminal A,LA)、腺腔B(luminal B,LB)、基底细胞样(basal-like,BL)和HER-2过表达(HER2-overexpressing,HER-2+)4种不同分子亚型乳腺癌中的蛋白表达和启动子甲基化状态及其与临床病理参数的关系。方法分别采用免疫组化SP法和甲基化特异性PCR(MSP)法检测88例乳腺癌组织中RUNX3基因蛋白表达和启动子甲基化水平,并分析其与临床病理参数的关系。结果 (1)LA、LB、HER-2+、BL型乳腺癌RUNX3蛋白阳性率分别为26.1%、45.0%、76.2%、75.0%;甲基化率分别为69.6%、85.0%、47.6%、29.2%。BL型的蛋白表达和甲基化率均与LA型、LB型差异均有显著性(P<0.05);HER-2+型蛋白表达与LA和LB差异有显著性(P<0.05),甲基化率与LB型差异有显著性(P<0.05)。(2)RUNX3蛋白阳性表达和阴性表达的乳腺癌患者中,RUNX3基因启动子甲基化率分别为36.7%、82.1%,差异有显著性(P<0.05)。(3)49例RUNX3阳性病例均见胞质表达,其细胞内定位在各亚型之间差异无显著性。(4)RUNX3基因启动子甲基化与组织学分级、临床分期相关(P<0.05),与淋巴结转移、肿块大小、患者年龄无关。结论 RUNX3蛋白表达缺失和启动子甲基化主要见于ER阳性乳腺癌,其蛋白胞质定位在乳腺癌中是普遍现象,可能与其功能异常相关,其启动子甲基化与乳腺癌传统预后因素相关。RUNX3基因蛋白表达缺失和启动子甲基化在BL型乳腺癌的发生、发展中可能不起主要作用。
Purpose To examine the RUNX3 gene promoter methylation and protein expression in 4 molecular subtypes of breast canc- er. Methods The promoter methylation and protein expression of RUNX3 gene were detected in 88 breast cancers using methylation specific PCR （MSP） and immunohistochemistry method respectively. Results （ 1 ） RUNX3 protein expression was 26. 1% , 45.0% , 76.2% and 75.0% , in luminal A （LA）, luminal B （LB）, HER-2 overexpressing （ HER-2 ＋ ） and basal-like （BL） phenotype re- spectively, and the methylation rate was 69.6% , 85.0% , 47.6% and 29. 2% respectively. The difference of RUNX3 expression and promoter methylation rate were significant between BL and both LA and LB tumors （ P 〈 0. 05 ） , the significant difference of RUNX3 expression was showed between HER-2 ＋ and both LA and LB tumors （ P 〈 0.05 ） , and the difference of RUNX3 methylation was sig- nificant compared with LB tumors （P 〈 0. 05）. （2） There was statistical difference on RUNX3 methylation between RUNX3 positive and negative tumors （36.7% vs 82. 1%, P 〈0. 05）. （3） All of the 49 RUNX3 positive cases showed cytoplasm positive, no differ- ence was found on RUNX3 protein intracellular localization between different subtypes. （4） RUNX3 promoter methylation was correla- ted to clinical stage and histological grade （P 〈 0.05 ） , but not correlated to lymph node metastasis, tumor size and patients＇ age. Conclusion Loss of RUNX3 protein expression and promoter methylation are mainly associated with ER positive breast cancers. Cyto- plasm localization is common pattern of RUNX3 protein expression in breast cancer, which may related to its dysfunction. RUNX3 methylation is associated with traditional prognostic factors in breast cancer. Loss of RUNX3 protein expression and its promoter methyl- ation may not play important roles in tumorgenesis and progression of BL.
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2014年第1期10-14,共5页
Chinese Journal of Clinical and Experimental Pathology
基金
江苏省卫生厅课题(H201020)
江苏省高校自然科学基金(10KJB310014)
