Adipose Triglyceride Lipase (ATGL) Expression Is Associated with Adiposity and Tumor Stromal Proliferation in Patients with Pancreatic Ductal Adenocarcinoma.

ABSTRACT

BACKGROUND: Obesity is an established risk factor for the development of pancreatic ductal adenocarcinoma (PDAC). However, the pathophysiology of how increased adiposity increases the risk for PDAC has not been fully elucidated. Adipose triglyceride lipase (ATGL) is a lipase that catabolizes triglyceride hydrolysis and has been implicated in the development of breast cancer. We hypothesized that overweight patients with PDAC would demonstrate higher tumor ATGL expression compared to non-overweight patients with PDAC. MATERIALS AND METHODS: Immunohistochemical analysis for ATGL expression was performed on PDAC tissues from 44 patients after Whipple procedure or distal pancreatectomy. Correlation of ATGL expression with clinicopathological features was evaluated. RESULTS: A total of 23/44 (52.2%) PDACs showed low level ATGL immunoreactivity, while 21/44 (47.8%) showed a high level, with moderate to strong positive ATGL immunoreactivity in more than 50% of the tumor cells. Chi-squared testing revealed a statistically significant association between high ATGL expression and both BMI >25 kg/m2 (χ2=5.74, p=0.017) and increased tumor stroma (χ2=19.14, p<0.001). Chi-squared testing failed to reveal a statistically significant association when comparing ATGL expression by lymph node metastasis, histological grade, tumor size, patient age, patient sex and presence of fat invasion. CONCLUSION: Our results suggest that increased ATGL expression is associated with increased adiposity and stromal proliferation in patients with PDAC, making it a possible key protein in how obesity increases the risk of PDAC.