1. Examining the carcinogenic potential of pancreatic inflammation in obese mice with maspin staining Janessa Pennington 1, Mariah Gawlik 1, Betty Herndon 1, Agostino Molteni 1, Tim Quinn 1, Alexey Glazyrin 1,2 1 UMKC School of Medicine, 2 Truman Medical Center Introduction Maspin (mammary serine protease inhibitor), is a member of the serine protease superfamily; It is down-regulated in breast and many other cancers but over-expressed in pancreatic, gallbladder, colorectal, and thyroid cancers suggesting that maspin may play different activities in different cell types. Maspin demonstrates both nuclear and cytoplasmic staining in pancreatic adenocarcinoma and ductal dysplasia. Weak stain appears in pancreatitis, and rare stain is seen in pancreatic dysplasia. Some expression is increased in inflammation. Several studies evaluate maspin in different tumor types in order to better define its prognostic significance, based on the differences in expression of maspin in various cancers. In this study we evaluated the correlation between maspin presence and pancreatic inflammation (strong in the OB/OB untreated group) and a group of OB/OB mice receiving a strong anti-inflammatory drug (TNFα-r blocker). Chronic pancreatitis is associated with inflammation and adenocarcinoma Unlike tumors in other sites, early pancreatic lesions upregulate maspin, a prognostic marker This study evaluates pancreatic pathology in an OB/OB mouse model, to determine if inflammation leads to pre-cancerous lesions that can be stained for maspin. Methods A 10 animal control group and a group receiving TNFα receptor blocker (n=10) were evaluated. Pancreas tissues collected at 2 months were stained by H&E and scored for inflammation and other damage. Anti-maspin labeling of pancxreas was used to determine proliferative changes. Inflammation and maspin staining were compared. Results H&E staining Liver & Pancreas Summary & Conclusions Our data suggests that pancreatic inflammation does not associate with anti-maspin staining in this model of liver steatosis and pancreatic damage Only the exocrine pancreatic ducts were highly inflamed on H&E staining Endocrine pancreas showed a significant anti- maspin staining in the Islets of Langerhans of untreated mice Endocrine pancreas of the TNFα-r blocker treated mice (strong anti-inflammatory action) showed a more accentuated anti-maspin staining, strengthening the premise that maspin presence is unrelated to inflammation in this model The relationship of maspin to other adipocytokines in the pancreas of this model remains an ongoing study References 1.Berardi et al, Role of Maspin in Cancer Clin & Translational Mwed 2:8, 2013 2.Koutsounas I et al, World J, Gastroenterology 19:813-828, 2013 The liver of untreated mice had the expected steatosis with mild inflammation 0f the portal triad (bile ducts, arteries, veins). Mild reduction was observed when the TNFα-r blocker was added to the diet H&E staining identified ductal inflammation in the exocrine (not endocrine) pancreas of untreated mice Inflammation was more evident in pancreatic ducts Arteries close to the ducts In portions of peri- pancreatic fat Anti-maspin staining in exocrine pancreas of mice showed a significant difference (p<0.05) 2.14 untreated 1.88 TNFα –r blocker Endocrine scores were also significantly different, (p=0.03) 4.75 untreated 7.43 TNFα –r blocker No differences occurred in serum insulin or blood glucose Untreated (left) and anti-inflammatory treated (right) OB/OB mouse livers, 100x and 400x Pancreas tissue of control and TNFα-r blocker- treated OB/OB mice Maspin staining-Pancreas Untreated OB/OB mice (left), Treated (right), maspin stain Note extensive fat infiltration in untreated mice livers, with severe infiltration in portal triads. Reduced inflammation with TNFα-r blocker. Necrosis of exocrine pancreas with duct inflammation in controls. Less maspin staining in control mouse Islets of Langerhans.