title: Cyclooxygenase-2 expression during carcinogenesis in the human stomach.
abstract: The prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with a reduced risk of gastric cancer. The best-known target of these drugs is cyclooxygenase (COX); the COX-2 isoform is frequently up-regulated in gastric adenocarcinomas. Using the post-gastrectomy stomach as a model, the expression of COX-2 mRNA and protein has been investigated during tumour progression in the human stomach. COX-2 expression was comparable in gastric stump carcinomas and conventional gastric carcinomas and localized primarily to the cytoplasm of the neoplastic cells. COX-2 mRNA was elevated in biopsies containing intestinal metaplasia, as determined by reverse transcriptase polymerase chain reaction (RT-PCR). COX-2 immunopositivity became more frequent during progression from reactive epithelium to high-grade dysplasia, both in the epithelial and in the stromal cell compartment. Co-localization of COX-2-positive stromal cells was seen with CD68, alpha-smooth muscle actin (alpha-SMA), vimentin, and HLA-DR, but an as yet unidentified subpopulation of stromal cells remained. Co-localization with the macrophage marker CD68 was only observed in a minority of COX-2-positive cells. These data show that COX-2 expression is a relatively early event during carcinogenesis in the stomach. COX-2 expression increases during tumour progression in the stomach, suggesting a role for COX-2 expression in gastric tumourigenesis.
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. b.p.vanrees@amc.uva.nl
authors.forename: Bastiaan P
authors.initials: BP
authors.lastname: van Rees
authors.forename: Kirsi
authors.initials: K
authors.lastname: Saukkonen
authors.forename: Ari
authors.initials: A
authors.lastname: Ristimäki
authors.forename: Wojciech
authors.initials: W
authors.lastname: Polkowski
authors.forename: Guido N J
authors.initials: GN
authors.lastname: Tytgat
authors.forename: Paul
authors.initials: P
authors.lastname: Drillenburg
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology*; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2; D003593:Cytoplasm / Q000201:enzymology; D018530:Gastric Stump; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007414:Intestinal Neoplasms / Q000201:enzymology* / Q000556:secondary*; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D011230:Precancerous Conditions / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000201:enzymology*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases