Abstract | BACKGROUND: 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.
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Authors | K N Khan, J L Masferrer, B M Woerner, R Soslow, A T Koki |
Journal | Scandinavian journal of gastroenterology
(Scand J Gastroenterol)
Vol. 36
Issue 8
Pg. 865-9
(Aug 2001)
ISSN: 0036-5521 [Print] England |
PMID | 11495083
(Publication Type: Journal Article)
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Chemical References |
- Isoenzymes
- Membrane Proteins
- Cyclooxygenase 1
- Cyclooxygenase 2
- PTGS1 protein, human
- PTGS2 protein, human
- Prostaglandin-Endoperoxide Synthases
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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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