Cyclooxygenase-2 expression during carcinogenesis in the human stomach

Bastiaan P. Van Rees, Kirsi Saukkonen, Ari Ristimki, Wojciech Polkowski, Guido N J Tytgat, Paul Drillenburg, G. Johan A Offerhaus

Research output: Contribution to journalArticlepeer-review

148 Scopus citations


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, α-smooth muscle actin (α-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.

Original languageEnglish (US)
Pages (from-to)171-179
Number of pages9
JournalJournal of Pathology
Issue number2
StatePublished - 2002
Externally publishedYes


  • Cancer
  • Carcinogenesis
  • Cyclooxygenase
  • Stomach
  • Tumour progression

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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