Euhus David M, Bu Dawei, Ashfaq Raheela, Xie Xian-Jin, Bian Aihua, Leitch A Marilyn, Lewis Cheryl M
E6.222, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9155, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1812-21. doi: 10.1158/1055-9965.EPI-06-1034.
Tumor suppressor gene (TSG) methylation is identified more frequently in random periareolar fine needle aspiration samples from women at high risk for breast cancer than women at lower risk. It is not known whether TSG methylation or atypia in nipple duct lavage (NDL) samples is related to predicted breast cancer risk.
514 NDL samples obtained from 150 women selected to represent a wide range of breast cancer risk were evaluated cytologically and by quantitative multiplex methylation-specific PCR for methylation of cyclin D2, APC, HIN1, RASSF1A, and RAR-beta2.
Based on methylation patterns and cytology, NDL retrieved cancer cells from only 9% of breasts ipsilateral to a breast cancer. Methylation of >/=2 genes correlated with marked atypia by univariate analysis, but not multivariate analysis, that adjusted for sample cellularity and risk group classification. Both marked atypia and TSG methylation independently predicted abundant cellularity in multivariate analyses. Discrimination between Gail lower-risk ducts and Gail high-risk ducts was similar for marked atypia [odds ratio (OR), 3.48; P = 0.06] and measures of TSG methylation (OR, 3.51; P = 0.03). However, marked atypia provided better discrimination between Gail lower-risk ducts and ducts contralateral to a breast cancer (OR, 6.91; P = 0.003, compared with methylation OR, 4.21; P = 0.02).
TSG methylation in NDL samples does not predict marked atypia after correcting for sample cellularity and risk group classification. Rather, both methylation and marked atypia are independently associated with highly cellular samples, Gail model risk classifications, and a personal history of breast cancer. This suggests the existence of related, but independent, pathogenic pathways in breast epithelium.
与乳腺癌低风险女性相比，在乳腺癌高风险女性的随机乳晕周围细针穿刺样本中，肿瘤抑制基因（TSG）甲基化的检出频率更高。目前尚不清楚乳头导管灌洗（NDL）样本中的TSG甲基化或异型性是否与预测的乳腺癌风险相关。
对从150名女性获取的514份NDL样本进行细胞学评估，并通过定量多重甲基化特异性PCR检测细胞周期蛋白D2、APC、HIN1、RASSF1A和RAR-β2的甲基化情况，这些女性代表了广泛的乳腺癌风险范围。
基于甲基化模式和细胞学检查，NDL仅从9%的乳腺癌同侧乳房中获取到癌细胞。单因素分析显示，≥2个基因的甲基化与明显异型性相关，但在多因素分析中不相关，多因素分析对样本细胞数量和风险组分类进行了校正。在多因素分析中，明显异型性和TSG甲基化均独立预测了丰富的细胞数量。对于明显异型性[比值比（OR），3.48；P = 0.06]和TSG甲基化指标（OR，3.51；P = 0.03），Gail低风险导管与Gail高风险导管之间的区分相似。然而，明显异型性在区分Gail低风险导管与乳腺癌对侧导管方面表现更好（OR，6.91；P = 0.
