乳腺导管内增生性病变及乳腺浸润性导管癌中TRβ1基因甲基化的研究

Methylation status of TRβ1 gene in intraductal proliferative lesions and invasive ductal carcinoma of breast

摘要:

目的：了解乳腺浸润性导管癌及乳腺导管增生性病变组织甲状腺素受体β1（thyroid hormone receptor β1，TRβ1）基因启动子区甲基化状态，探讨其与乳腺癌发生的关系。方法：采用甲基化特异性PCR（methylation-specific polymerase chain reaction，MSP）技术，研究40例乳腺浸润性导管癌（infiltrating ductal carcinoma，IDC）、12例普通型导管增生（usual ductal hyperplasia，UDH）、8例乳腺不典型性导管增生（atpical ductal hyperplasia，ADH），24例导管原位癌（duetal carcinoma in situ，DCIS）组织及10例健康成人女性乳腺组织中TRβ1基因启动子区甲基化状态。结果：正常乳腺组织、UDH、ADH、DCIS和IDC中，TRβ1基因甲基化率分别为0.0%（0/10）、16.7%（2/12）、37.5%（3/8）、62.5%（15/24）和80.0%（32/40），正常组织TRβ1基因甲基化率与DCIS和IDC相比差异有统计学意义（P正常组对DCIS=0.001，P正常组对IDC=0.000）；UDH与DCIS相比，差异无统计学意义（P=0.009）；UDH与IDC相比差异有统计学意义（P=0.000）。结论：TRβ1基因启动子区CpG岛甲基化是乳腺癌发生过程中的早期事件，可能在乳腺癌发生和乳腺增生病癌变过程中起重要生物学作用。

Abstract:

Objective：To understand promoter methylation status of thyroid hormone receptor β1（TRβ1） gene in intraductal prolifera－tive lesions and invasive ductal carcinoma of breast and to discuss its relationship with breast cancer. Methods：By methylation-spe－cific polymerase chain reaction（MSP），we detected promoter methylation status of TRβ1 gene in mammary tissues of 40 cases of in－filtrating ductal carcinoma（IDC），12 cases of usual ductal hyperplasia（UDH），8 cases of atpical ductal hyperplasia（ADH），24 cases of duetal carcinoma in situ（DCIS） and 10 cases of healthy adult women. Results：Methylation rates of TRβ1 gene were 0.0%（0/10），16.7%（2/12），37.5%（3/8），62.5%（15/24） and 80.0%（32/40） in healthy breast，UDH，ADH，DCIS，and IDC respectively. There were significant differences in methylation rate of TRβ1 gene between healthy breast and DCIS，IDC（P=0.001，P=0.000）. There was no sta－tistical difference in methylation rate of TRβ1 gene between UDH and DCIS（P=0.009）. There were statistical differences in methyla－tion rate of TRβ1 gene between UDH and IDC（P=0.000）. Conclusions：Promoter methylation of TRβ1 gene is an early event in the development of breast carcinoma and may play an important biological role in breast carcinogenesis.