Human colorectal adenomas demonstrate a size-dependent increase in epithelial cyclooxygenase-2 expression
Article first published online: 20 SEP 2002
Copyright © 2002 John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 198, Issue 4, pages 428–434, December 2002
How to Cite
Elder, D. J., Baker, J. A., Banu, N. A., Moorghen, M. and Paraskeva, C. (2002), Human colorectal adenomas demonstrate a size-dependent increase in epithelial cyclooxygenase-2 expression. J. Pathol., 198: 428–434. doi: 10.1002/path.1232
- Issue published online: 13 NOV 2002
- Article first published online: 20 SEP 2002
- Manuscript Accepted: 13 MAY 2002
- Manuscript Revised: 10 MAY 2002
- Manuscript Received: 26 FEB 2002
- UK Cancer Research Campaign. Grant Number: SP1949/1202
Non-steroidal anti-inflammatory drugs are chemopreventive for colorectal cancer. This effect is due in part to their ability to inhibit the inducible isoform of cyclooxygenase (COX-2). However, the cellular expression and role of COX-2 in the premalignant stages of colorectal tumourigenesis is unclear. COX-2 expression was assessed in 35 human colorectal adenomas and 38 sporadic invasive colorectal adenocarcinomas. Adenomas were classified as small (<5 mm in diameter), medium (5–10 mm), and large (>10 mm). All tissues were paraffin-embedded and formalin-fixed. COX-2 protein expression was determined using immunohistochemistry. COX-2 was detected in the epithelial cells in 35 of 38 carcinomas (92%) and in 8 of 8 (100%) lymph node metastases. All of the epithelial cells expressed COX-2 in 30 of 35 (86%) carcinomas and in 100% of the lymph node metastases. Twenty-three of 35 (66%) adenomas expressed COX-2 in the tumour epithelium. With an increase in the size of adenoma (<5 mm, 5–10 mm, >10 mm), there was an increase in (i) the proportion of adenomas with immunoreactive COX-2 in the epithelium (p = 0.036)—this was 38% in small adenomas and 82% in large adenomas; (ii) the extent of epithelial COX-2 staining within a given tumour (p = 0.003)—100% of epithelial cells were COX-2-positive in 15% of small adenomas and in 73% of large adenomas; and (iii) the intensity of epithelial COX-2 staining (p = 0.009)—strong COX-2 staining occurred in 8% of small adenomas and in 36% of large adenomas. COX-2 immunoreactivity was not detected in adjacent normal epithelium but was apparent in fibroblasts and inflammatory mononuclear cells of adjacent normal, adenoma, and carcinoma tissue. These results suggest that epithelial COX-2 activity is important for the growth and/or survival of adenomatous epithelial cells from an adenoma diameter of less than 5 mm and that there is a selective advantage for adenoma epithelial cells expressing higher levels of COX-2. Copyright © 2002 John Wiley & Sons, Ltd.