Clinical implications of ERβ methylation on sporadic breast cancers in Chinese women.

Estrogens play a key role in the genesis and progression of breast cancer, activating two estrogen receptors, alpha and beta (ERα and ERβ). We have previously observed that ERα methylation occurs in high frequency and may be one of the mechanisms of ERα expression silence in a subset of Chinese sporadic breast cancers. However, the ERβ promoter methylation status and the relationship between clinicopathological characteristics and ERβ methylation in sporadic breast cancer are still unknown, especially in Chinese women. This study acted to determine the methylation status of the ERβ promoter and its correlation with clinicopathological features of sporadic breast cancers in Chinese women, and lay a foundation for the management of breast cancer. In total, 178 cases with sporadic breast cancers were enrolled in the study. ERβ methylation was determined using a methylation-specific polymerase chain reaction (MSP). In general, ERβ promoter methylation was found in 44.9% (80/178) of breast tumor samples, significantly higher than the benign breast hyperplasia (44.9% vs. 14.3%, X(2) = 4.986, P = 0.026). A total of 58% (40/69) of ERβ-negative tumors got methylation compared with 36.7% (40/109) of ERβ-positive cases being methylated (X(2) = 7.728, P = 0.005). The levels of ERβ protein expression diminished with the frequency of ERβ methylation (r = -0.249, P < 0.0001). In addition, we observed a strong correlation between ERα promoter and ERβ promoter methylation (odds ratio 2.054, 95% confidence interval 1.086-3.886, P = 0.026), and the triple-negative tumors showed a significantly higher methylation rate of ERβ. This study presents, for what we believe to be the first time, that ERβ methylation is also a frequent event in breast cancer and maybe also one of the mechanisms of ERβ expression silence in a subset of Chinese sporadic breast cancers. Epigenetic alteration of the ERβ gene may play an important role in the pathogenesis of breast cancer.