Peritumoral Expression of Adipokines and Fatty Acids in Breast Cancer
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Adipokines in the tumor microenvironment may contribute to cancer growth. We hypothesized that peritumoral fat can be a source of lipid-derived energy for tumors by increasing adipose triglyceride lipase (ATGL)-mediated lipolysis and down-regulating a negative regulator of adipogenesis, pigment epithelium-derived factor (PEDF).
In a pilot study, tissue from mastectomies (n = 19) was collected from sites both adjacent (peritumoral) and distant to the tumor for comparison of ATGL, PEDF, and leptin expression levels using immunohistochemistry. Statistical analysis was performed by Student’s t test to determine significance.
Mean tumor size was 2.4 cm, and 10 (59 %) patients had tumor-positive nodes. Mean body mass index (BMI) was 28.1 kg/m2. ATGL expression was significantly increased in obese patients (BMI ≥30 kg/m2) compared with the nonobese group (P < 0.04). Leptin expression was increased in the peritumoral stroma of obese patients compared with distant sites (P = 0.03). Peritumoral PEDF and the leptin/PEDF ratio were significantly affected by tumor size and node status. Tumors ≥2 cm had lower peritumoral stromal expression of PEDF than tumors <2 cm (P = 0.01). In node-positive cases, expression of PEDF was significantly decreased in the peritumoral stroma compared with node-negative cases (1.22 vs. 1.80, P < 0.04). The leptin/PEDF ratio was markedly elevated in the peritumoral region of node-positive cases versus node-negative cases (2.17 vs. 1.18, P < 0.001).
Peritumoral expression of adipokines was altered in both obesity and more advanced breast tumors, suggesting a role for adipokines in enhancing tumor growth. Future studies should focus on the use of adipokines as biomarkers.
KeywordsNonobese Patient Contralateral Prophylactic Mastectomy Exogenous Fatty Acid Adipose Triglyceride Lipase Synchronous Bilateral Breast Cancer
Supported by the Auxiliary of Evanston and Glenbrook Hospital’s Breast and Ovarian Research Pilot Award, NorthShore University HealthSystem.
The authors declare no conflict of interest.
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