Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2008 Jan 29:8:33.
doi: 10.1186/1471-2407-8-33.

Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma

Takako Kawasaki  1 , Katsuhiko Nosho, Mutsuko Ohnishi, Yuko Suemoto, Jonathan N Glickman, Andrew T Chan, Gregory J Kirkner, Mari Mino-Kenudson, Charles S Fuchs, Shuji Ogino
Affiliations
Comparative Study

Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma

Takako Kawasaki et al. BMC Cancer. .

Abstract

Background: Cyclooxygenase-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.

Methods: By 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.

Results: Strong (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 (approximately 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.

Conclusion: COX-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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Histopathology of serrated colorectal neoplasias. A. Sessile serrated polyp/adenoma (SSA) with abnormal crypt architecture (flat-based crypt) (arrow). B. Mixed polyp with SSA (empty arrowhead) and non-serrated adenoma (empty arrow). C. traditional serrated adenoma with abundant eosinophilic cytoplasm of epithelial cells. D. Colorectal adenocarcinoma with serration (arrows).
Figure 2
Figure 2
Immunohistochemistry for COX-2 in colorectal neoplasias. A. No overexpression in colorectal adenoma (arrow). Inflammatory cells serve as an internal positive control (empty arrow). B. Weak (1+) overexpression in colorectal adenoma (arrows). C. Strong (2+) overexpression in colorectal adenoma (arrows). Note a junction between adenoma and normal appearing colon (empty block arrow). D. Strong (2+) overexpression in colorectal adenocarcinoma (arrows).
Figure 3
Figure 3
Frequency of strong (2+) COX-2 overexpression in various colorectal neoplasias.
Figure 4
Figure 4
Frequency of any (1+ or 2+) COX-2 overexpression in various colorectal neoplasias.
See this image and copyright information in PMC

References

    1. Brown JR, DuBois RN. COX-2: a molecular target for colorectal cancer prevention. J Clin Oncol. 2005;23:2840–2855. doi: 10.1200/JCO.2005.09.051. - DOI - PubMed
    1. Sheehan KM, O'Connell F, O'Grady A, Conroy RM, Leader MB, Byrne MF, Murray FE, Kay EW. The relationship between cyclooxygenase-2 expression and characteristics of malignant transformation in human colorectal adenomas. Eur J Gastroenterol Hepatol. 2004;16:619–625. doi: 10.1097/00042737-200406000-00017. - DOI - PubMed
    1. Larkins TL, Nowell M, Singh S, Sanford GL. Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. BMC Cancer. 2006;6:181. doi: 10.1186/1471-2407-6-181. - DOI - PMC - PubMed
    1. Klenke FM, Gebhard MM, Ewerbeck V, Abdollahi A, Huber PE, Sckell A. The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: an intravital microscopy study in mice. BMC Cancer. 2006;6:9. doi: 10.1186/1471-2407-6-9. - DOI - PMC - PubMed
    1. Fux R, Schwab M, Thon KP, Gleiter CH, Fritz P. Cyclooxygenase-2 expression in human colorectal cancer is unrelated to overall patient survival. Clin Cancer Res. 2005;11:4754–4760. doi: 10.1158/1078-0432.CCR-04-2586. - DOI - PubMed

Publication types