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Immunohistochemical analysis of adipokine and adipokine receptor expression in the breast tumor microenvironment: associations of lower leptin receptor expression with estrogen receptor-negative status and triple-negative subtype

  • Llanos, Adana A. M.1, 2
  • Lin, Yong1, 2
  • Chen, Wenjin2, 3
  • Yao, Song4
  • Norin, Jorden2, 5
  • Chekmareva, Marina A.2, 3
  • Omene, Coral2, 3
  • Cong, Lei2
  • Omilian, Angela R.4
  • Khoury, Thaer4
  • Hong, Chi-Chen4
  • Ganesan, Shridar2, 3, 3
  • Foran, David J.2, 3
  • Higgins, Michael4
  • Ambrosone, Christine B.4
  • Bandera, Elisa V.1, 2
  • Demissie, Kitaw6
  • 1 Rutgers School of Public Health, Piscataway, NJ, USA , Piscataway (United States)
  • 2 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA , New Brunswick (United States)
  • 3 Robert Wood Johnson Medical School, New Brunswick, NJ, USA , New Brunswick (United States)
  • 4 Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA , Buffalo (United States)
  • 5 Rutgers School of Arts and Sciences, New Brunswick, NJ, USA , New Brunswick (United States)
  • 6 SUNY Downstate Health Sciences University School of Public Health, Brooklyn, NY, USA , Brooklyn (United States)
Published Article
Breast Cancer Research
BioMed Central
Publication Date
Feb 11, 2020
DOI: 10.1186/s13058-020-1256-3
Springer Nature


BackgroundThe 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).MethodsWe 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.ResultsLarger 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.ConclusionsLower 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.

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