Peritumoral Expression of Adipokines and Fatty Acids in Breast Cancer

Abstract

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/m(2). ATGL expression was significantly increased in obese patients (BMI ≥ 30 kg/m(2)) 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.