Endocrine biomarkers in ductal lavage samples from women at high risk for breast cancer
Endocrine biomarkers in ductal lavage samples from women at high risk for breast cancer
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DOI：
10.1158/1055-9965.epi-05-0302
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发表时间：
2005-11-01
影响因子：
3.8
通讯作者：
Khan, SA
中科院分区：
文献类型：
--
作者：
Bhandare, D;Nayar, R;Khan, SA
背景资料：导管灌洗是一种对乳房进行最少上皮取样的方法，在化学预防研究中具有重复取样和生物标志物分析的潜在效用。我们在这里报告的基线结果，从一项研究，旨在评估实用性的导管灌洗在此setting.Methods：他莫昔芬合格，高风险的妇女进行导管灌洗;上皮细胞数量（ECN）和形态进行了评估巴氏染色的幻灯片。对其他载玻片进行雌激素受体（ER）α、Ki-67和环氧合酶-2免疫染色，并通过计数阴性和阳性细胞建立标记指数（LI）。导管灌洗液上清液（DLS）测定雌二醇，其前体，孕酮，组织蛋白酶D，白细胞介素-6，和表皮生长因子（EGF）。结果：一百六十八名妇女已进入研究（平均年龄，51岁，平均5年盖尔评分，2.8）。145名（86.3%）妇女完成了导管灌洗。按导管和女性分析数据（所有导管的平均数据）。145例女性中有43例（29.6%）出现轻度妊娠，而2例（1.4%）出现重度妊娠。我们观察到ECN与细胞学指标、ER LI、COX-2 LI和Ki-67 LI呈显著正相关。EGF水平与雌激素前体、ER LI和ECN显著相关。代表DLS激素和蛋白质变量的一个因素解释了36%的方差;总ECN是最高的因素得分和ER LI高，最低时，两者都低（P的相互作用= 0.001）。结论：生物标志物分析上皮细胞和DLS是可行的。EGF与其他标志物的显着关联表明在增加上皮细胞质量中可能起作用。
Background: Ductal lavage is a method of minimal epithelial sampling of the breast, with potential utility for repeat sampling and biomarker analysis in chemoprevention studies. We report here the baseline findings from a study designed to assess the utility of ductal lavage in this setting.Methods: Tamoxifen-eligible, high-risk women underwent ductal lavage; epithelial cell number (ECN) and morphology were assessed on Papanicolaou-stained slides. Additional slides were immunostained for estrogen receptor (ER) alpha, Ki-67, and cyclooxygenase-2, and the labeling index (LI) was established by counting negative and positive cells. The ductal lavage supernatant (DLS) was assayed for estradiol, several of its precursors, progesterone, cathepsin D, interleukin-6, and epidermal growth factor (EGF).Results: One hundred sixty-eight women have entered the study (mean age, 51 years; mean 5-year Gail score, 2.8). Ductal lavage was accomplished in 145 (86.3%) women. Data were analyzed by duct and by woman (averaging data across all ducts). Mild atypia was seen in 43 of 145 (29.6%), whereas severe atypia was seen in 2 (1.4%) of women. We observed significant positive correlations between ECN and cytologic atypia, ER LI, cyclooxygenase-2 LI, and Ki-67 LI. EGF levels in supernatant were significantly associated with estrogenic precursors, ER LI and ECN. A factor representing the DLS hormone and protein variables explained 36% of the variance; total ECN was highest when factor score and ER LI were high and was lowest when both were low (P for interaction = 0.001).Conclusions: Biomarker analyses in epithelial cells and DLS are feasible. The significant associations of EGF with other markers suggest a possible role in increasing epithelial cell mass.