University of Florida, College of Public Health and Health Professions and College of Medicine, Department of Epidemiology, Gainesville, FL, USA.
Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Br J Cancer. 2024 Jul;131(2):325-333. doi: 10.1038/s41416-024-02743-2. Epub 2024 Jun 7.
We examined associations of CD44, CD24 and ALDH1A1 breast stem cell markers with mammographic breast density (MBD), a well-established breast cancer (BCa) risk factor.
We included 218 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII. The data on BCa risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was done on tissue microarrays. For each core, the IHC expression was assessed using a semi-automated platform and expressed as percent of positively stained cells for each marker out of the total cell count. MBD was assessed with computer-assisted techniques. Generalised linear regression was used to examine the associations of each marker with square root-transformed percent density (PD), absolute dense and non-dense areas (NDA), adjusted for BCa risk factors.
Stromal CD44 and ALDH1A1 expression was positively associated with PD (≥ 10% vs. <10% β = 0.56, 95% confidence interval [CI] [0.06; 1.07] and β = 0.81 [0.27; 1.34], respectively) and inversely associated with NDA (β per 10% increase = -0.17 [-0.34; -0.01] and β for ≥10% vs. <10% = -1.17 [-2.07; -0.28], respectively). Epithelial CD24 expression was inversely associated with PD (β per 10% increase = -0.14 [-0.28; -0.01]. Stromal and epithelial CD24 expression was positively associated with NDA (β per 10% increase = 0.35 [0.2 × 10; 0.70] and β per 10% increase = 0.34 [0.11; 0.57], respectively).
Expression of stem cell markers is associated with MBD.
我们研究了 CD44、CD24 和 ALDH1A1 乳腺癌干细胞标志物与乳腺密度(MBD)的相关性,MBD 是一种已确立的乳腺癌(BCa)风险因素。
我们纳入了 218 名在护士健康研究(NHS)和 NHSII 中经活检证实患有良性乳腺疾病且无癌症的女性。BCa 风险因素的数据来自于每两年一次的问卷调查。免疫组织化学(IHC)在组织微阵列上进行。对于每个核心,使用半自动平台评估 IHC 表达,并表示为每个标志物的阳性染色细胞百分比与总细胞计数之比。MBD 使用计算机辅助技术进行评估。使用广义线性回归来检查每个标志物与平方根转换后的密度百分比(PD)、绝对致密和非致密区域(NDA)的关系,调整了 BCa 风险因素。
基质 CD44 和 ALDH1A1 的表达与 PD(≥10%与 <10%,β=0.56,95%置信区间[CI]为[0.06;1.07]和β=0.81[0.27;1.34])呈正相关,与 NDA 呈负相关(每增加 10%的β=-0.17[-0.34;-0.01]和≥10%与 <10%的β=-1.17[-2.07;-0.28])。上皮 CD24 的表达与 PD 呈负相关(每增加 10%的β=-0.14[-0.28;-0.01])。基质和上皮 CD24 的表达与 NDA 呈正相关(每增加 10%的β=0.35[0.2×10;0.70]和β=0.34[0.11;0.57])。
干细胞标志物的表达与 MBD 相关。