Suijkerbuijk Karijn P M, van der Wall Elsken, Vooijs Marc, van Diest Paul J
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Pathobiology. 2008;75(2):149-52. doi: 10.1159/000123853. Epub 2008 Jun 10.
Lack of sensitivity and specificity of image-based breast cancer screening has urged the exploration of alternate screening modalities. Nipple fluid, which contains breast epithelial cells, is produced in small amounts in the breast ducts of nonlactating women and can be collected by noninvasive vacuum aspiration. After administration of nasal oxytocin, nipple aspiration yields sufficient material for molecular analysis in the large majority of women. Whereas nipple fluid cytology appears to have only a moderate correlation with breast cancer development, methylation holds promise as a more appropriate biomarker, since methylation aberrations occur as an early and frequent event during carcinogenesis. Using quantitative multiplex methylation-specific PCR, methylation can be detected in minute amounts of DNA extracted from nipple aspirates, precluding the need for more invasive intraductal approaches such as ductal lavage and random periareolar fine needle aspiration. The application of genomic and proteomic diagnostics to nipple aspirates therefore provides unprecedented opportunities for early breast cancer diagnosis amendable to population-based screening.
基于图像的乳腺癌筛查缺乏敏感性和特异性，促使人们探索其他筛查方式。乳头液由乳腺上皮细胞组成，在非哺乳期女性的乳腺导管中少量产生，可通过无创真空抽吸收集。给予鼻腔催产素后，大多数女性通过乳头抽吸可获得足够用于分子分析的材料。虽然乳头液细胞学检查与乳腺癌发生的相关性似乎一般，但甲基化有望成为更合适的生物标志物，因为甲基化异常是致癌过程中早期且常见的事件。使用定量多重甲基化特异性PCR，可在从乳头抽吸物中提取的微量DNA中检测到甲基化，无需采用如导管灌洗和随机乳晕周围细针穿刺等更具侵入性的导管内方法。因此，将基因组和蛋白质组诊断应用于乳头抽吸物为适用于人群筛查的早期乳腺癌诊断提供了前所未有的机会。
