Abstract
BackgroundCyclooxygenase-2 (COX-2, PTGS2) plays an important role in colorectal carcinogenesis. COX-2 overexpression in colorectal cancer is inversely associated with microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). Evidence suggests that MSI/CIMP+ colorectal cancer may arise through the serrated tumorigenic pathway through various forms of serrated neoplasias. Therefore, we hypothesized that COX-2 may play a less important role in the serrated pathway.MethodsBy immunohistochemistry, we assessed COX-2 expression in 24 hyperplastic polyps, 7 sessile serrated polyp/adenomas (SSA), 5 mixed polyps with SSA and adenoma, 27 traditional serrated adenomas, 515 non-serrated adenomas (tubular adenoma, tubulovillous adenoma and villous adenoma), 33 adenomas with intramucosal carcinomas, 96 adenocarcinomas with serration (corkscrew gland) and 111 adenocarcinomas without serration.ResultsStrong (2+) COX-2 overexpression was more common in non-serrated adenomas (28% = 143/515) than in hyperplastic polyps (4.2% = 1/24, p = 0.008) and serrated polyps (7 SSAs and 5 mixed polyps) (0% = 0/12, p = 0.04). Furthermore, any (1+/2+) COX-2 overexpression was more frequent in non-serrated adenomas (60% = 307/515) than in hyperplastic polyps (13% = 3/24, p < 0.0001) and serrated polyps (SSAs and mixed polyps) (25% = 3/12, p = 0.03). Traditional serrated adenomas and non-serrated adenomas showed similar frequencies of COX-2 overexpression. Regardless of serration, COX-2 overexpression was frequent (~85%) in colorectal adenocarcinomas. Tumor location was not significantly correlated with COX-2 overexpression, although there was a trend towards higher frequencies of COX-2 overexpression in distal tumors (than proximal tumors) among hyperplastic polyps, SSAs, mixed polyps, traditional serrated adenomas and adenocarcinomas.ConclusionCOX-2 overexpression is infrequent in hyperplastic polyp, SSA and mixed polyp with SSA and adenoma, compared to non-serrated and serrated adenoma. COX-2 overexpression becomes more frequent as tumors progress to higher grade neoplasias. Our observations suggest that COX-2 may play a less significant role in the serrated pathway of tumorigenesis; however, COX-2 may still play a role in later stage of the serrated pathway.
Highlights
Cyclooxygenase-2 (COX-2, PTGS2) plays an important role in colorectal carcinogenesis
COX-2 overexpression is infrequent in hyperplastic polyp, sessile serrated polyp/adenoma (SSA) and mixed polyp with Sessile serrated polyp/adenoma (SSA) and non-serrated adenoma There were totals of 605 colorectal polyps and adenomas, including 24 hyperplastic polyps (HPs), 7 sessile serrated polyp/adenomas (SSAs), 5 mixed polyps (MPs) with SSA and non-serrated adenoma, 27 traditional serrated adenomas (SAs), 393 tubular adenomas, 109 tubulovillous adenomas, 13 villous adenomas, and 33 adenomas with intramucosal adenocarcinoma
Among all 605 colorectal polyps and adenomas, weak (1+) COX-2 overexpression was observed in 191 cases (32%), and strong (2+) COX-2 overexpression was observed in 160 cases (26%)
Summary
Cyclooxygenase-2 (COX-2, PTGS2) plays an important role in colorectal carcinogenesis. Cyclooxygenase-2 (COX-2 or PTGS2, the HUGOapproved official gene symbol) has been considered to have an important role in the development of various cancers, including colorectal cancer [1,2,3,4]. COX-2 selective inhibitor celecoxib inhibits the growth of colorectal cancer cells in vitro [11,12]. COX-2 is a promising chemopreventive target against colorectal neoplasia [1,16,17] In light of these observations, it may be important to examine COX-2 expression levels in precursor lesions to predict effectiveness of chemoprevention by COX-2 inhibition [10,18]
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