Human colorectal adenomas demonstrate a size-dependent increase in epithelial cyclooxygenase-2 expression.
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.
Elder
Douglas J E
DJ
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol, UK.
Baker
Jenny A
JA
Banu
Nahida A
NA
Moorghen
Moganaden
M
Paraskeva
Christos
C
D000230:Adenocarcinoma / Q000201:enzymology; D000236:Adenoma / Q000201:enzymology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D018450:Disease Progression; D004847:Epithelial Cells / Q000201:enzymology; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases