BACKGROUND The molecular mechanisms underlying the association between increased adiposity and aggressive breast cancer phenotypes remain unclear, but likely involve the adipokines, leptin (LEP) and adiponectin (ADIPOQ), and their receptors (LEPR, ADIPOR1, ADIPOR2). METHODS We used immunohistochemistry (IHC) to assess LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 expression in breast tumor tissue microarrays among a sample of 720 women recently diagnosed with breast cancer (540 of whom self-identified as Black). We scored IHC expression quantitatively, using digital pathology analysis. We abstracted data on tumor grade, tumor size, tumor stage, lymph node status, Ki67, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) from pathology records, and used ER, PR, and HER2 expression data to classify breast cancer subtype. We used multivariable mixed effects models to estimate associations of IHC expression with tumor clinicopathology, in the overall sample and separately among Blacks. RESULTS Larger proportions of Black than White women were overweight or obese and had more aggressive tumor features. Older age, Black race, postmenopausal status, and higher body mass index were associated with higher LEPR IHC expression. In multivariable models, lower LEPR IHC expression was associated with ER-negative status and triple-negative subtype (P < 0.0001) in the overall sample and among Black women only. LEP, ADIPOQ, ADIPOR1, and ADIPOR2 IHC expression were not significantly associated with breast tumor clinicopathology. CONCLUSIONS Lower LEPR IHC expression within the breast tumor microenvironment might contribute mechanistically to inter-individual variation in aggressive breast cancer clinicopathology, particularly ER-negative status and triple-negative subtype.

中文翻译：

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乳腺肿瘤微环境中脂肪因子和脂肪因子受体表达的免疫组织化学分析：低瘦素受体表达与雌激素受体阴性状态和三阴性亚型的关联。

背景 肥胖增加与侵袭性乳腺癌表型之间关联的分子机制尚不清楚，但可能涉及脂肪因​​子、瘦素 (LEP) 和脂联素 (ADIPOQ) 及其受体 (LEPR、ADIPOR1、ADIPOR2)。方法 我们使用免疫组织化学 (IHC) 来评估最近诊断出患有乳腺癌的 720 名女性（其中 540 名自我认定为黑人）的乳腺肿瘤组织微阵列中 LEP、LEPR、ADIPOQ、ADIPOR1 和 ADIPOR2 的表达。我们使用数字病理学分析对 IHC 表达进行定量评分。我们从病理记录中提取了肿瘤分级、肿瘤大小、肿瘤分期、淋巴结状态、Ki67、雌激素受体 (ER)、孕激素受体 (PR) 和人表皮生长因子受体 2 (HER2) 的数据，并使用了 ER、PR , 和 HER2 表达数据以对乳腺癌亚型进行分类。我们使用多变量混合效应模型来估计 IHC 表达与肿瘤临床病理学、整体样本中和黑人之间的关联。结果 与白人女性相比，黑人女性超重或肥胖的比例更大，并且具有更具侵袭性的肿瘤特征。年龄较大、黑人、绝经后状态和较高的体重指数与较高的 LEPR IHC 表达相关。在多变量模型中，较低的 LEPR IHC 表达与 ER 阴性状态和三阴性亚型 (P < 0.0001) 在整个样本中和仅在黑人女性中相关。LEP、ADIPOQ、ADIPOR1 和 ADIPOR2 IHC 表达与乳腺肿瘤临床病理学无显着相关性。