Tierärztliche Hochschule Hannover - TiHo Bibliothek elib

8. Summary
Till Erben: “Detection of Calprotectin and Reg3A proteins in inflammatory and neoplastic
disease of the pancreas”
Human Calprotectin, a complex formed by the S100A8 and S100A9 proteins is expressed in
neutrophils and monocytes migrated into inflammatory pancreatic tissue. This study
demonstrated expression by pancreatic carcinoma cell line CAPAN-1 and HUP-T4 by
screening cell lysates in Western-blot analyses and whole cells in immunolabeling studies.
Moreover S100A9 was detected in vivo by immunolabeling in human tissue of a poorly
differentiated ductal adenocarcinoma of the pancreas whereas well differentiated
adenocarcinoma did not show S100A9 expression. The plasma S100A8/A9 levels were
sensitively up regulated in patients with ductal adenocarcinoma (sensitivity 89,7%; specificity
82,7%) compared to healthy controls. Surprisingly detection of chronic pancreatitis by
Calprotectin was less sensitive (sensitivity 73,5% ; specificity 80%). However it is still
unclear how Calprotectin is secreted into plasma fluids by leucocytes.
Physiological pancreatic tissue expresses Reg3A protein associated to the membrane of
zymogen granules. Overexpression of Reg3A in patients suffering from chronic pancreatitis
leads to secretion into pancreatic fluids where high amounts of the protein can be detected all
over the pancreatic duct system by immunolabeling. In case of severe tissue injury Reg3A
was associated to a broad range of membranous structures – for example vacuoles of
degenerating acinar cells, cell membranes and at last associated to the endothelium of
capillaries and veins in inflammatory tissue. Reg3A is up regulated in plasma of patients with
pancreatic disease. Blood plasma levels indicate chronic pancreatitis (sensitivity 81,6% ;
specificity 76,3%) compared to healthy controls. Above that it is a sensitive indicator for
ductal adenocarcinoma of the pancreas (sensitivity 93,1 % ; specificity 70%). Both proteins,
human Calprotectin as well as Reg3A are insufficient in differentiation of chronic pancreatitis
and adenocarcinoma of the pancreas. Reg3A and Calprotectin are sensitive indicators of
ductal adenocarcinoma and may be of value in combination with the more specific commonly
used CA19-9 marker (sensitivity 81%; specificity 90%). Reg3A and S100A8/A9 plasma
levels in pancreatic disease have to be opposed to the levels of these proteins detected in other
gastrointestinal disease.
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