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Enhanced cyclooxygenase-2 expression in sporadic and familial adenomatous polyposis of the human colon.

AbstractBACKGROUND:
The cyclooxygenase (COX) enzymes exist in two related but unique isoforms (COX-1 and COX-2) and catalyze the formation of prostaglandins (PGs). COX-1 is constitutively expressed, and is responsible for the synthesis of PGs necessary for gastroprotection and normal renal function. The COX-2 isoform is important in a variety of pathophysiological conditions such as inflammation and tumorigenesis. Numerous studies report that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) can decrease the incidence of some tumor types, including gastrointestinal polyposis.
METHODS:
In this study, we evaluated COX-1 and COX-2 expression in 30 polyps collected from 10 patients with familial adenomatous polyposis (FAP) and in 18 polyps collected from 18 patients with sporadic adenomatous polyposis (SAP) using COX-1 or COX-2 isoform-specific antibodies. All tissues were formalin-fixed and paraffin-embedded. Immunoreactivity was detected using tyramide signal amplification and evaluated utilizing an immunohistochemical scoring system.
RESULTS:
COX-2 was minimally detected in the distant non-neoplastic epithelium, which also served as an internal negative control. In comparison, all polyps collected from SAP or FAP patients overexpressed COX-2 in the neoplastic epithelial cells (P < or = 0.002). Additionally, pronounced COX-2 expression was observed in the stromal cells underlying and adjacent to adenomatous lesions. COX-1 immunoreactivity was weak to mild throughout each tissue evaluated and did not change in the neoplastic or stromal cells of the polyps.
CONCLUSIONS:
COX-2 expression is upregulated in the adenomatous epithelium of SAP and FAP, while the COX-1 isoform appears to be constitutively expressed at low levels in both neoplastic and non-neoplastic regions. The differential expression of COX-1 and COX-2 in these neoplasms suggests that COX-2 rather than COX-1 may play a role in adenoma formation and/or growth in cases of SAP and FAP in humans.
AuthorsK N Khan, J L Masferrer, B M Woerner, R Soslow, A T Koki
JournalScandinavian journal of gastroenterology (Scand J Gastroenterol) Vol. 36 Issue 8 Pg. 865-9 (Aug 2001) ISSN: 0036-5521 [Print] England
PMID11495083 (Publication Type: Journal Article)
Chemical References
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
Topics
  • Adenomatous Polyposis Coli (enzymology, pathology)
  • Adult
  • Aged
  • Aged, 80 and over
  • Colonic Neoplasms (enzymology, pathology)
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Isoenzymes (analysis, immunology)
  • Male
  • Membrane Proteins
  • Middle Aged
  • Prostaglandin-Endoperoxide Synthases (analysis, immunology)
  • Up-Regulation

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