目的: 探讨ER基因5'CpG岛甲基化在原发性乳腺癌组织中与ER蛋白失表达的关系及其在肿瘤进展中的作用。方法: 用限制性酶PCR检测45例乳腺浸润性导管癌及15例乳腺良性病变雌激素受体(estrogen receptor,ER)基因中5'CpG岛甲基化状态,甲基化检测结果与免疫组织化学方法检测的ER蛋白表达结果进行比较。结果: 在45例乳腺浸润性导管癌中,有20例发生甲基化(44%),其中4例在2个酶切位点均发生甲基化,而其他的只在HpaⅡ位点发生甲基化。15例乳腺良性病变中,无1例发生甲基化。82%ER阳性的乳腺癌组织显示在ER基因中HpaⅡ、HhaⅠ位点均未发生甲基化,而61%ER阴性的乳腺癌组织显示在ER基因中HpaⅡ和(或)HhaⅠ位点发生甲基化,提示免疫组化ER蛋白表达与ER基因5'CpG呈负相关(P<0.05)。结论: 人类乳腺浸润性导管癌中ER基因的5'CpG岛的甲基化与ER蛋白的表达呈负相关,且随组织学分级升高,甲基化发生率增加。

Objective: The present study aimed to investigate the correlation between 5'CpG island methylation status of estrogen receptor(ER) gene and negative expression of ER protein in primary breast cancer tissues and discuss its role in tumorigenesis. Methods: DNA was extracted from 45 cases of primary breast carcinomas and 15 cases of benign breast lesions. The status of 5'CpG island methylation in ER gene was detected by methylation-specific polymerase chain reaction(MSP) and compared with ER protein expression evaluated by immunohistochemistry. Results: The CpG island methylaion was detected in the 20 breast invasive ductal carcinomas(20/45, 44%) including methylation at two sites(4 cases) and methylation at Hpa Ⅱ site(16 cases). The CpG island methylaion was not detected in 15 cases of breast benign lesions. Methylation of ER gene at Hpa Ⅱ and(or) Hha I site was not detected in 82% of ER-positive breast cancer tissues but was detected in 61% of ER-negative breast cancer tissues(P<0.05). Conclusion: Methylation of the CpG island of the ER gene was inversely correlated with ER protein expression in human breast invasive ductal carcinoma. The frequency of methylation was increased with the elevation of histological grade of breast carcinoma.