Expression of Antioxidant Enzymes in Diseases of the Human Pancreas: Another Link Between Chronic Pancreatitis and Pancreatic Cancer

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Abstract
Chronic pancreatitis is a significant risk factor for pancreatic cancer and is associated with the generation of reactive oxygen species. Cells contain a large number of antioxidants to prevent or repair the damage caused by reactive oxygen species. There are three major types of primary intracellular antioxidant enzymes in mammalian cells: superoxide dismutase (SOD), catalase, and peroxidase, of which glutathione peroxidase is the most prominent. To determine the level of antioxidant enzymes in human pancreas from normal, chronic pancreatitis, and pancreatic cancer specimens. Immunohistochemical analysis for manganese SOD, copper/zinc SOD, catalase, and glutathione peroxidase expression using the avidin–biotin–peroxidase complex method was performed on pancreatic specimens previously fixed in formalin and embedded in paraffin. A quantitative digital imaging methodology was used to examine antioxidant staining in the pancreatic tissue. Cytoplasmic regions of ductal and acinar cells were identified and digitized. Mean gray-level pixel values were then obtained for each of these regions. Cytoplasmic values of manganese SOD, catalase, and glutathione peroxidase were decreased in pancreatic cells from chronic pancreatitis specimens when compared with normal pancreas. In pancreatic carcinoma specimens, mean cytoplasmic gray-level values of all antioxidant enzymes were decreased when compared with normal pancreas. There appears to be a gradual decrease in antioxidant enzyme expression in pancreatic cells from normal pancreas to chronic pancreatitis to pancreatic cancer.