Cyclooxygenase 2 expression in chronic pancreatitis: Correlation with stage of the disease and diabetes mellitus

Background: Fibrotic replacement of the exocrine pancreatic parenchyma and infiltration of inflammatory cells are the main characteristics of chronic pancreatitis (CP). Inflammation involves prostaglandin production in numerous inflammatory and noninflammatory cells, and cyclooxygenase 2 (COX-2) is the dominant regulator of prostaglandin synthesis. Aims: In the present study, we analyzed the expression of COX-2, the key enzyme for prostaglandin synthesis in pancreatic tissues, and evaluated its relation to exocrine and endocrine tissue alterations in CP. Patients and Methods: Pancreatic tissue specimens from 27 patients undergoing pancreatic head resection for CP were included in the study. Pancreatic tissues from 14 organ donors served as controls. The tissue specimens were analyzed histopathologically and for COX-2 immunoreactivity. Results: In normal pancreatic tissue samples, COX-2 immunoreactivity was restricted to islet cells. In contrast, in early-stage CP, islets as well as ductal cells showed intense COX-2 immunoreactivity. In advanced-stage CP, ductal cells were still strongly positive for COX-2, yet islets displayed a variable COX-2 staining pattern which was associated with the distribution of insulin-positive cells and with the clinical diabetes mellitus status of the patient. Thus, patients with normal or latent diabetes mellitus status showed COX-2 immunoreactivity, whereas in diabetic patients the COX-2 immunoreactivity was decreased or absent in pancreatic islets. Conclusion: The presence of COX-2 in ductal cells of early and advanced CP, the relationship between COX-2 and insulin expression in the islets, and the diabetes mellitus status of CP patients suggest that this enzyme plays a role in the pathogenesis of exocrine and endocrine damage in CP.