Crown-like structures in breast adipose tissue of breast cancer patients: associations with CD68 expression, obesity, metabolic factors and prognosis

• Published in: NPJ breast cancer 2021-07, Vol.7 (1), p.97-97, Article 97
• Main Authors: Chang, Martin C., Eslami, Zohreh, Ennis, Marguerite, Goodwin, Pamela J.
• Format: Article
• Language: English
• Subjects: 631/67/2327; 692/4028/67/1347; 692/499; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cell Biology; Human Genetics; Insulin; Medical prognosis; Metabolism; Obesity; Oncology
• ISSN: 2374-4677; 2374-4677
• DOI: 10.1038/s41523-021-00304-x

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 χ 2 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.