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

Enhanced cyclooxygenase-2 expression in sporadic and familial adenomatous polyposis of the human colon
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DOI:
10.1080/003655201750313405
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发表时间:
2001-08-01
影响因子:
1.9
通讯作者:
Koki, AT
Koki, AT
中科院分区:
医学4区
文献类型:
--
作者:
Khan, KNM;Masferrer, JL;Koki, AT

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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 less than or equal to 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 nonneoplastic 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.