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


CONCLUSIONS
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.
Kawasaki
Takako
T
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. takako_kawasaki@dfci.harvard.edu
Nosho
Katsuhiko
K
Ohnishi
Mutsuko
M
Suemoto
Yuko
Y
Glickman
Jonathan N
JN
Chan
Andrew T
AT
Kirkner
Gregory J
GJ
Mino-Kenudson
Mari
M
Fuchs
Charles S
CS
Ogino
Shuji
S
D000236:Adenoma / Q000201:enzymology* / Q000235:genetics; D000368:Aged; D015331:Cohort Studies; D003111:Colonic Polyps / Q000201:enzymology* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D006965:Hyperplasia / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human