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



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.



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.



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.
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, MO, U.S.A.
Shane A
SA
Grace
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, MO, U.S.A.
Marshall W
MW
Meeks
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, MO, U.S.A.
Yongxin
Y
Chen
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, MO, U.S.A.
Mona
M
Cornwell
Department of Pathology, Loyola University Medical Center, Maywood, IL, U.S.A.
Xianzhong
X
Ding
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, MO, U.S.A.
Ping
P
Hou
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, U.S.A.
Joanne K
JK
Rutgers
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, MO, U.S.A.
Susan E
SE
Crawford
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, MO, U.S.A. jinpinglai@slu.edu.
Jin-Ping
JP
Lai
D050154:Adiposity; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008049:Lipase / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010180:Pancreatectomy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000217:Acyltransferases
D014408:Biomarkers, Tumor; D008049:Lipase; C494794:PNPLA2 protein, human; D000217:Acyltransferases
ATGL; Adipose triglyceride lipase; PDAC; obesity; pancreatic ductal adenocarcinoma