[1521] The Role of the Soluble Epoxide Hydrolase Expression and K55R Genetic Polymorphism in Pancreatic Ductal Adenocarcionma.

Xianzhong Ding, Jie Liao, Haonan Li, M Sambasiva Rao, Seth Krantz, David Bentrem, Guang-Yu Yang. Northwestern University, Chicago, IL

Background: Many studies have shown strong association between inflammation and pancreatic tumorigenesis. The soluble epoxide hydrolase (sEH) is an enzyme participating in arachidonic metabolism, particularly metabolism of endogenous signal and inflammatory mediators, 20--HETE (hydroxyeicosatrienoic acid) and EETs (epoxyeicosatrienoic acid). sEH is a 62-Kd protein containing a 35-kd C-termianl domain with epoxide hydrolase activity and a 25-kd N-terminal domain with phosphatase activity. Further, Enzyme activity of sEH is modified by the K55R genetic polymorphism, which is a risk factor for the development of coronary heart disease due to increased systemic inflammation. However the role of sEH in pancreatic carcinogenesis has never been studied. Because strong association between inflammation and pancreatic tumorigenesis, it is conceivable that pancreatic cancer development and progress might be preceded by disregulated sEH expression and activity.
Design: sEH expression was evaluated from pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (28 cases) and chronic pancreatitis (19 cases) including sections containing PanIN (pancreatic intraepithelial neoplasia) lesions by immunohistochemistry. The sEH staining was classified as no staining (0), low intensity staining (+) or high intensity staining (++). K55R genetic polymorphism was evaluated in 70 pancreatic ductal adenocarcinoma specimen by PCR and DNA sequencing.
Results: Distinct over-expression of sEH was identified in infiltrating pancreatic ductal adenocarcinoma compared to normal, chronic pancreatitis, fibrotic, and PanIN lesions. 96% (27/28) pancreatic ductal adenocarcinoma showed strong cytoplasmic sEH staining. Three cases (15%) of chronic pancreatitis showed mild staining in chronic inflammatory cells and reactive stromal cells. 6 PanIN lesions (mainly PanIN I and II lesions) were negative for sEH. No positive staining was identified in normal pancreatic ductal epithelial cells, acinar cells and islets. sEH K55R single nucleotide DNA polymorphism was identified in 11% (8/70) of pancreatic ductal adenocarcinoma.
Conclusions: This study demonstrated significant over-expression of sEH in human infiltrating pancreatic ductal adenocarcinoma, indicating it may serve as a useful biomarker to differentiate pancreatic ductal adenocarcinoma from pre-malignant lesions. The K55R genetic polymorphism is detected in human pancreatic cancer. It further warrants exploring the role of up-regulated soluble epoxide hydrolase expression and sEH polymorphism in pancreatic carcinogenesis.
Category: Liver & Pancreas

Tuesday, March 1, 2011 1:00 PM

Poster Session IV # 212, Tuesday Afternoon

 

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