Monahan Denise A, Wang Jun, Lee Oukseub, Revesz Elizabeth, Taft Nancy, Ivancic David, Hansen Nora M, Bethke Kevin P, Zalles C, Khan Seema A
John H. Stroger Hospital of Cook County, Rush University Medical Center, Chicago, IL, USA.
Department of Surgery, USA.
Surg Oncol. 2016 Dec;25(4):449-456. doi: 10.1016/j.suronc.2015.12.001. Epub 2015 Dec 30.
The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients.
83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression.
Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = -0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = -0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1.
Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development.
单侧乳腺癌女性的对侧未受影响乳房（CUB）为研究基于乳腺组织的风险因素提供了一个模型。我们使用随机细针穿刺抽吸（rFNA），研究了新诊断乳腺癌患者CUB中与异型性相关的激素和基因表达模式。
83名女性接受了CUB的rFNA。使用马苏德评分（MS）进行细胞学分析，异型性定义为MS>14。使用80%的样本提取RNA。使用Taqman低密度阵列对20个激素相关基因的表达进行定量。使用双侧t检验和线性回归进行统计分析。
经产妇的细胞学异型性更常见（P = 0.0392），且与患侧乳房的任何肿瘤相关特征均无关。自上次怀孕以来间隔时间越短，马苏德评分越高（R = 0.204，P = 0.0417），分娩次数越多评分越高（R = 0.369，P = 0.0006），且指数癌的雌激素受体（ER）阴性时评分越高（R = -0.203，P = 0.065）。个体细胞学特征与产次方面相关。具体而言，核仁大小不一与自上次怀孕以来间隔时间越短相关（R = 0.318，P = 0.0201），与分娩次数越多相关（R = 0.382，P = 0.0004），且与ER状态相关（R = -0.314，P = 0.0038）。在非典型样本中，8个雌激素调节基因表达增加（P < 0.005），包括TFF1、AGT、PDZK1、PGR、GREB1、PRLR、CAMK2B和CCND1。
细胞学异型性，尤其是核仁大小不一，与近期多次分娩及指数肿瘤的ER阴性状态相关。非典型样本显示雌激素相关基因表达增加，这与雌激素暴露在乳腺癌发生中的作用一致。
