Expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic adenocarcinoma: correlation with microvessel density.
OBJECTIVE
Cyclooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins. Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible isoforms. The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis, tumorigenesis and inflammatory processes. This study was to clarify their role in pancreatic adenocarcinomas.


METHODS
We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocarcinomas of different grade and stage. The results were compared with microvessel density and clinicopathological data.


RESULTS
Twenty-one (52.5%) of the cases showed iNOS expression, 15 (37.5%) of the cases were positive for COX-2. The immunoreaction was heterogeneously distributed within the tumors. Staining intensity was different between the tumors. No correlation between iNOS and COX-2 expression was seen. There was no relationship with microvessel density. However, iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression. There was no correlation with other clinicopathological data.


CONCLUSIONS
Approximately half of the cases expressed iNOS and COX-2. These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas. Due to a low prevalence of COX-2 expression, chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success.
Kasper
Hans-U
HU
Department of Pathology, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50931 Koeln, Germany. hans-udo.kasper@uni-koeln.de
Wolf
Hella
H
Drebber
Uta
U
Wolf
Helmut-K
HK
Kern
Michael-A
MA
D000230:Adenocarcinoma / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008833:Microcirculation; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010179:Pancreas / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases