Enhanced cyclooxygenase-2 expression in sporadic and familial adenomatous polyposis of the human colon.
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.
Khan
K N
KN
Pharmacia Research and Development, Skokie, IL, USA. nasir.k.khan@monsanto.com
Masferrer
J L
JL
Woerner
B M
BM
Soslow
R
R
Koki
A T
AT
D011125:Adenomatous Polyposis Coli / Q000201:enzymology* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000276:immunology; D015854:Up-Regulation
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases