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Crown-like structures in breast adipose tissue of breast cancer patients: associations with CD68 expression, obesity, metabolic factors and prognosis
npj Breast Cancer ( IF 6.5 ) Pub Date : 2021-07-22 , DOI: 10.1038/s41523-021-00304-x
Martin C Chang 1, 2 , Zohreh Eslami 3 , Marguerite Ennis 4 , Pamela J Goodwin 5, 6
Affiliation  

Crown-like structures of the breast (CLS-B), defined by the clustering of macrophages (identified using CD68 immunohistochemical staining) to surround a dying adipocyte, are a sign of adipose-tissue inflammation. In human cohorts, CLS-B positively correlates with older age, obesity, dyslipidemia and higher levels of glucose, insulin, C-reactive protein and IL-6. In an existing cohort of early-stage breast cancer patients, CLS-B were identified using H&E stained histologic sections (hCLS-B), and by CD68 immunohistochemistry (CD68 + CLS-B). We examined associations of H&E and CD68-detected CLS-B with clinicopathologic features using χ2 tests, with metabolic factors using Wilcoxon rank sum tests and with disease free and overall survival using Cox regression models. hCLS-B were detected in 59 of 163 patients with slides (36.2%) and CD68 + CLS-B in 37 of 119 patients with paraffin blocks (31.1%). hCLS-B were positively correlated with higher weight (p = 0.003), BMI (p = 0.0008) and C-reactive protein (p = 0.045). CD68 + CLS-B were positively correlated with higher weight (p = 0.006), BMI p = 0.001), leptin (p = 0.034), insulin (p = 0.008) and Homeostasis Model Assessment (p = 0.027). CD68 + CLS-B were associated with poor distant disease-free with a hazard ratio (HR) of 2.81, 95% confidence interval (CI) 1.20–6.57, and overall survival with HR 3.97 (1.66–9.48), while hCLS-B were not associated with either: HR for distant recurrence 0.59 (0.26–1.30); HR for death 1.04 (0.50–2.16). The presence of hCLS-B and of CD68 + CLS-B were associated with obesity; CD68 + CLS-B were associated with insulin resistance and adverse prognosis. Similar patterns were not seen for hCLS-B. Research is needed to understand the biologic basis for these differences.



中文翻译:


乳腺癌患者乳腺脂肪组织中的冠状结构:与CD68表达、肥胖、代谢因素和预后的关系



乳房的冠状结构 (CLS-B) 是由巨噬细胞聚集(使用 CD68 免疫组织化学染色鉴定)包围垂死的脂肪细胞来定义的,是脂肪组织炎症的标志。在人类队列中,CLS-B 与老年、肥胖、血脂异常以及较高水平的葡萄糖、胰岛素、C 反应蛋白和 IL-6 呈正相关。在现有的早期乳腺癌患者队列中,使用 H&E 染色组织学切片 (hCLS-B) 和 CD68 免疫组织化学 (CD68 + CLS-B) 来鉴定 CLS-B。我们使用χ2检验检查了 H&E 和 CD68 检测到的 CLS-B 与临床病理特征的关联,使用 Wilcoxon 秩和检验检查了代谢因素的关联,并使用 Cox 回归模型检查了 H& E和 CD68 检测到的 CLS-B 与无病生存和总生存的关联。在 163 名载玻片患者中的 59 名 (36.2%) 中检测到 hCLS-B,在 119 名石蜡块患者中的 37 名 (31.1%) 中检测到 CD68 + CLS-B。 hCLS-B 与较高的体重 ( p = 0.003)、BMI ( p = 0.0008) 和 C 反应蛋白 ( p = 0.045) 呈正相关。 CD68 + CLS-B 与较高体重 ( p = 0.006)、BMI ( p = 0.001)、瘦素 ( p = 0.034)、胰岛素 ( p = 0.008) 和稳态模型评估 ( p = 0.027) 呈正相关。 CD68 + CLS-B 与较差的远处无病相关,风险比 (HR) 为 2.81,95% 置信区间 (CI) 1.20–6.57,总生存率 HR 为 3.97 (1.66–9.48),而 hCLS-B与以下两者均无关: 远处复发的 HR 0.59 (0.26–1.30);死亡 HR 1.04 (0.50–2.16)。 hCLS-B 和 CD68 + CLS-B 的存在与肥胖相关; CD68 + CLS-B 与胰岛素抵抗和不良预后相关。 hCLS-B 中没有观察到类似的模式。需要进行研究来了解这些差异的生物学基础。

更新日期:2021-07-22
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