摘要
目的探讨散发性乳腺癌中BRCA l基因异常甲基化状况及其与蛋白表达的关系,进而研究散发性乳腺癌中BRCA l基因异常的表遗传学作用。方法用甲基特异性聚合酶链反应(PCR)和免疫组织化学(SP)法研究乳腺癌组织、癌旁正常组织中BRCA l基因启动子甲基化状况及蛋白表达情况。结果在52例散发性乳腺癌中,BRCA l甲基化率为29%,BRCA l蛋白表达下降率为33%;15例BRCA l发生甲基化的癌组织标本中BRCA l的表达下降率为87%,而37例BRCA l未发生甲基化的癌组织中BRCA l蛋白表达下降率11%。在肿瘤分级中,T3分级患者的肿瘤组织中BRCA l甲基化率(45%)及表达下降率(60%)均分别高于T1+T2分级患者肿瘤组织的BRCA l甲基化率(19%)和表达下降率(16%);有淋巴结转移患者的肿瘤组织中BRCA l甲基化率(46%)及蛋白表达下降率(50%)均分别高于无淋巴结转移的甲基化率(14%)和表达下降率(18%)。结论BRCA l基因表遗传学改变是其蛋白表达下降乃至失活的重要原因,并且与散发性乳腺癌的恶性进程和淋巴结转移密切相关。
Objective To study the status of hypermethylated BRCA1 gene promoter regions and expression level of BRCA1 protein,and to research the epigenetics role of aberrant BRCA1 gene in sporadic breast cancer. Methods Methylation specific polymerase chain reaetion（PCR） was used to study the hypermethylation status of BRCA1 promoter regions and immunostaining was performed to analyze protein expression of BRCA1 in earcinous tissue and adjacent normal tissue of sporadic breast cancer. Results Hypermethylation frequencies of BRCA1 gene were 29% and reduced expression rates of BRCAI protein were 33% in 52 sporadic breast caneer; Reduced expression rates of BRCAI protein were 87% in 15 cases of malignant tissue which showed BRCA1 hypermethylated ,while there was only 11% reduced expression of BRCAI protein when BRCA1 gene kept unmethylated status in careinous tissue. Hypermethylation rates（45% ） of BRCAI and its expressional reducation rates （60%） of T3 tumor grade were higher than that of TI plus T2 tumor grades （19% and 16% ） respectively;Hypermethylation rates （46%） of BRCA1 gene and reduced expression rates （50%） of BRCA1 protein were also higher in the lymph node metastasis than thai of without lymph node metastasis （ 14% and 18%）. Conclusions Epigenetics alterations of the BRCA1 gene can contribute to reducing or losing expression of BRCAI protein,which play an important role in the development of sporadic breast carcinoma and may be involved in lympth node metastasis.
出处
《检验医学》
CAS
北大核心
2006年第6期642-646,共5页
Laboratory Medicine
