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Early expression of cyclo‐oxygenase‐2 during sporadic colorectal carcinogenesis
Author(s) -
Hao Xingpei,
Bishop Anne E.,
Wallace Marina,
Wang Hong,
Willcocks Teresa C.,
Maclouf Jacques,
Polak Julia M.,
Knight Stella,
Talbot Ian C.
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199902)187:3<295::aid-path254>3.0.co;2-y
Subject(s) - hyperplastic polyp , immunohistochemistry , adenoma , pathology , colorectal cancer , carcinogenesis , medicine , carcinoma , dysplasia , cancer , colonoscopy
Regular administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) may reduce the incidence of colorectal cancer by targeting cyclo‐oxygenase‐2 (Cox‐2), a key enzyme in arachidonic acid metabolism. To evaluate the role of Cox‐2 in sporadic colorectal cancer development, Cox‐2 expression was investigated by immunohistochemistry in 85 adenomas, 53 carcinomas, 34 hyperplastic lesions and 104 samples of histologically normal mucosa adjacent to adenoma or carcinoma. In addition, Cox‐2 mRNA expression was assessed by reverse transcription‐polymerase chain reaction (RT‐PCR) in six adenomas and 14 carcinomas with paired grossly normal mucosa. Immunohistochemistry for the proliferation‐associated antigen Ki‐67 and in situ end labelling for demonstrating apoptotic bodies were also used to analyse the associations between Cox‐2 expression and proliferation and apoptosis. Cox‐2 protein expression was increased in 76/85 (89·4 per cent) adenomas and 44/53 (83·0 per cent) carcinomas compared with normal mucosa. Cox‐2 protein expression was unrelated either to the degree of dysplasia or to the size of the adenomas ( p > 0·50, p > 0·10, respectively) or to differentiation, Dukes stage or lymph node metastasis of carcinomas (all p > 0·50). Interestingly, 20/34 (58·8 per cent) hyperplastic lesions adjacent to adenomas or carcinomas displayed expression higher than in normal mucosa (18·3 per cent) ( p < 0·0001) but lower than in adenomas or carcinomas ( p < 10 −5 , p < 0·001, respectively). There were no correlations between Cox‐2 protein expression and proliferative or apoptotic index in either adenomas or carcinomas (all p > 0·25). Cox‐2 mRNA expression was significantly increased in adenomas and carcinomas compared with normal mucosa ( p < 0·005, p < 0·001, respectively). There were no differences between adenomas and carcinomas in either protein or mRNA levels ( p > 0·25, p > 0·90, respectively). These data indicate that enhanced expression of Cox‐2 occurs early during colorectal carcinogenesis and may contribute to tumour formation. Copyright © 1999 John Wiley & Sons, Ltd.