Yaghjyan Lusine, Heng Yujing J, Baker Gabrielle M, Murthy Divya, Mahoney Matt B, Rosner Bernard, Tamimi Rulla M
Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida Gainesville, FL, USA.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, MA, USA.
Am J Cancer Res. 2023 Dec 15;13(12):6280-6289. eCollection 2023.
We examined associations of stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsy samples with subsequent breast cancer (BCa) risk and explored if these associations were mediated by mammographic breast density (MBD). We included 101 BCa cases/375 controls, all with previous biopsy-confirmed benign breast disease (BBD) within the Nurses' Health Study (NHS) and NHSII. The data on BCa risk factors were obtained from biennial questionnaires. MBD was assessed with computer-assisted techniques. Immunohistochemistry (IHC) was done on BBD tissue microarrays. For each core, the IHC expression was assessed using a semi-automated method, and expressed as % of cells that stained positive for a specific marker out of the total cell count. Logistic regression was used to examine the associations of each marker's expression of each (in epithelium and stroma) with BCa risk, adjusted for risk factors. Stromal CD44 expression was inversely associated with BCa risk (OR for ≥10% vs. <10%=0.58, 95% CI 0.34, 1.00). Combined stromal + epithelial CD24 expression was inversely associated with BCa risk (>50% vs. 0-10% OR=0.17, 95% CI 0.04-0.81, p-trend =0.03). Stromal CD24 and ALDH1A1 as well as epithelial expression of any of the three markers were not associated with BCa risk. In a smaller subset of women with available MBD, these observed associations did not appear to be mediated by MBD. Our findings suggest inverse associations of CD44 in stroma and combined stromal + epithelial CD24 with BCa risk. Future studies are warranted to confirm our findings and to examine these associations by BBD subtype.
我们研究了良性乳腺活检样本中干细胞标志物CD44、CD24和ALDH1A1与后续患乳腺癌（BCa）风险之间的关联，并探讨了这些关联是否由乳腺X线摄影密度（MBD）介导。我们纳入了101例BCa病例/375例对照，所有病例均在护士健康研究（NHS）和NHSII中曾有活检确诊的良性乳腺疾病（BBD）。BCa危险因素的数据通过两年一次的问卷调查获得。MBD采用计算机辅助技术进行评估。对BBD组织芯片进行免疫组织化学（IHC）检测。对于每个组织芯块，采用半自动方法评估IHC表达，并表示为特定标志物染色阳性的细胞占总细胞数的百分比。采用逻辑回归分析来检验每种标志物在（上皮和基质中）的表达与BCa风险之间的关联，并对危险因素进行校正。基质CD44表达与BCa风险呈负相关（≥10% vs. <10%的比值比=0.58，95%可信区间0.34，1.00）。基质+上皮CD24联合表达与BCa风险呈负相关（>50% vs. 0-10%的比值比=0.17，95%可信区间0.04-0.81，p趋势=0.03）。基质CD24和ALDH1A1以及这三种标志物中任何一种的上皮表达与BCa风险均无关联。在一小部分有可用MBD数据的女性中，这些观察到的关联似乎不是由MBD介导的。我们的研究结果表明，基质中的CD44以及基质+上皮CD24联合表达与BCa风险呈负相关。未来的研究有必要证实我们的发现，并按BBD亚型来研究这些关联。
