Visvanathan Kala, Cimino-Mathews Ashley, Fackler Mary Jo, Karia Pritesh S, VandenBussche Christopher J, Orellana Mikiaila, May Betty, White Marissa J, Habibi Mehran, Lange Julie, Euhus David, Stearns Vered, Fetting John, Camp Melissa, Jacobs Lisa, Sukumar Saraswati
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Women's Malignancy Program, Johns Hopkins Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Breast J. 2022 Aug 11;2022:9533461. doi: 10.1155/2022/9533461. eCollection 2022.
Critical regulatory genes are functionally silenced by DNA hypermethylation in breast cancer and premalignant lesions. The objective of this study was to examine whether DNA methylation assessed in random fine needle aspirates (rFNA) can be used to inform breast cancer risk.
In 20 women with invasive breast cancer scheduled for surgery at Johns Hopkins Hospital, cumulative methylation status was assessed in a comprehensive manner. rFNA was performed on tumors, adjacent normal tissues, and all remaining quadrants. Pathology review was conducted on blocks from all excised tissue. The cumulative methylation index (CMI) for 12 genes was assessed by a highly sensitive QM-MSP assay in 280 aspirates and tissue from 11 incidental premalignant lesions. Mann-Whitney and Kruskal Wallis tests were used to compare median CMI by patient, location, and tumor characteristics.
The median age of participants was 49 years (interquartile range [IQR]: 44-58). DNA methylation was detectable at high levels in all tumor aspirates (median CMI = 252, IQR: 75-111). Methylation was zero or low in aspirates from adjacent tissue (median CMI = 11, IQR: 0-13), and other quadrants (median CMI = 2, IQR: 1-5). Nineteen incidental lesions were identified in 13 women (4 malignant and 15 premalignant). Median CMI levels were not significantly different in aspirates from quadrants ( = 0.43) or adjacent tissue ( = 0.93) in which 11 methylated incidental lesions were identified.
The diagnostic accuracy of methylation based on rFNA alone to detect premalignant lesions or at-risk quadrants is poor and therefore should not be used to evaluate cancer risk. A more targeted approach needs to be evaluated.
关键调控基因在乳腺癌及癌前病变中因DNA高甲基化而功能沉默。本研究的目的是检验在随机细针穿刺抽吸物（rFNA）中评估的DNA甲基化是否可用于判断乳腺癌风险。
在约翰霍普金斯医院计划接受手术的20名浸润性乳腺癌女性患者中，以综合方式评估累积甲基化状态。对肿瘤、邻近正常组织及所有其余象限进行rFNA。对所有切除组织的石蜡块进行病理检查。通过高灵敏度的QM-MSP检测法评估280份抽吸物及来自11例偶然发现的癌前病变组织中12个基因的累积甲基化指数（CMI）。采用Mann-Whitney检验和Kruskal Wallis检验，按患者、部位及肿瘤特征比较CMI中位数。
参与者的年龄中位数为49岁（四分位间距[IQR]：44 - 58）。在所有肿瘤抽吸物中均可检测到高水平的DNA甲基化（CMI中位数 = 252，IQR：75 - 111）。邻近组织抽吸物中的甲基化为零或水平较低（CMI中位数 = 11，IQR：0 - 13），其他象限的抽吸物中甲基化水平也较低（CMI中位数 = 2，IQR：1 - 5）。在13名女性中发现了19例偶然病变（4例恶性和15例癌前病变）。在发现11例甲基化偶然病变的象限（P = 0.43）或邻近组织（P = 0.93）的抽吸物中，CMI中位数水平无显著差异。
仅基于rFNA检测癌前病变或有风险象限的甲基化诊断准确性较差，因此不应将其用于评估癌症风险。需要评估更具针对性的方法。
