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(American Journal of Pathology. 2000;156:545-553.)
© 2000 American Society for Investigative Pathology

Regular Articles

Localization of Cyclooxygenase-2 in Human Sporadic Colorectal Adenomas

Keith S. Chapple*, Elizabeth J. Cartwright*, Gillian Hawcroft*, Alison Tisbury*, Constanze Bonifer*, Nigel Scott{dagger}, Alistair C. J. Windsor{ddagger}, Pierre J. Guillou{ddagger}, Alexander F. Markham*, P. Louise Coletta* and Mark A. Hull*

From the Molecular Medicine Unit,*
the Department of Histopathology,{dagger}
and the Department of Surgery,{ddagger}
University of Leeds, St. James’s University Hospital, Leeds, United Kingdom

A putative target for the anti-colorectal cancer action of nonsteroidal anti-inflammatory drugs is the inducible isoform of cyclooxygenase (COX), COX-2. COX-2 is expressed within intestinal adenomas in murine polyposis models, but expression has been poorly characterized in human colorectal neoplasms. Therefore, we investigated the localization of the COX-2 protein in human sporadic colorectal adenomas. Immunohistochemistry for COX-2 and CD68 (a tissue macrophage marker) was performed on formalin-fixed, paraffin-embedded (n = 52) and frozen, acetone-fixed (n = 6) sections of human sporadic colorectal adenomas. Forty of 52 (77%) formalin-fixed adenomas expressed immunoreactive COX-2. COX-2 was localized to superficial interstitial macrophages in 39 cases (75%) and to deep interstitial macrophages in 9 cases (17%). COX-2 staining of dysplastic epithelial cells was observed in 15 cases (29%). A logistic regression analysis identified the adenoma site (P = 0.012) and histological type (P = 0.001) as independent predictors of superficial macrophage COX-2 expression. There was no relationship between the number of macrophages within an adenoma and macrophage COX-2 expression. These results indicate that COX-2 is expressed predominantly by interstitial macrophages within human sporadic colorectal adenomas. If COX-2 does indeed play a role in the early stages of colorectal carcinogenesis in man, these data suggest COX-2-mediated paracrine signaling between the macrophages and epithelial cells within adenomas.




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