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Association between Cyclooxygenase Expression and Colorectal Adenoma Characteristics¹

Arizona Cancer Center [J. G. E., M. E. M., D. S. A.], Department of Surgery [R. S. K.], and Department of Surgical Pathology, Arizona Health Sciences Center [A. K. B.], University of Arizona, Tucson, Arizona 85724; Southern Arizona Veterans Affairs Health Care System, Tucson, Arizona 85723 [R. S. K.]; Response Genetics, Los Angeles, California 90033 [J. M. Y., K. D. D.]; and [J. M. Y., K. D. D.], Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center [P. V. D.], University of Southern California, Los Angeles, California 90033

The cyclooxygenase (COX) pathway is important in colorectal carcinogenesis with the majority of cancers overexpressing COX-2; however, the role of COX-2 in the development of colorectal adenomas is less well defined. Accordingly, we analyzed 108 colorectal adenomas for COX-1 and COX-2 transcription in archival formalin-fixed, paraffin-embedded tissue using by real-time PCR and normalized to ß-actin. Neither COX-1 nor COX-2 mRNA expression differed with regard to age or gender of the subject. COX-2 mRNA expression was significantly higher in distal adenomas (2.2 ± 1.9) compared with proximal (0.7 ± 0.5) adenomas (P < 0.0001) and in larger (7 mm) compared with smaller (<7 mm) adenomas (2.3 ± 2.2 and 1.7 ± 1.3, respectively, P = 0.04). COX-2 expression did not differ significantly in tubular compared with tubulovillous adenomas, although there appeared to be a trend toward higher COX-2 expression in tubulovillous adenomas with increasing villous content. Additionally, there was not a significant difference in either COX-1 or COX-2 based on the degree of dysplasia Therefore, if COX-2 inhibitors work through a COX-2 mechanism, these agents may have differential effects on colorectal adenomas that are distal and larger.

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