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

Adana A.M. Llanos, Yong Lin, Wenjin Chen, Song Yao, Jorden Norin, Marina A. Chekmareva, Coral Omene, Lei Cong, Angela R. Omilian, Thaer Khoury, Chi Chen Hong, Shridar Ganesan, David J. Foran, Michael Higgins, Christine B. Ambrosone, Elisa V. Bandera, Kitaw Demissie

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number18
JournalBreast Cancer Research
Volume22
Issue number1
DOIs
StatePublished - Feb 11 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Adiponectin
  • Adiponectin receptors 1 and 2
  • Aggressive tumor features
  • Breast cancer clinicopathology
  • IHC expression
  • Leptin
  • Leptin receptor

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