title: Cyclooxygenase (COX)-2 immunoreactivity and relationship to p53 and Ki-67 expression in colorectal cancer.
abstract: The tumor-suppressive effects of nonsteroidal antiinflammatory drugs (NSAIDs) have been suggested to be due to a reduction in cyclooxygenase (COX)-2 activity, although the effects of COX-2 in the colonic mucosa and in colorectal cancer have not been determined. Ki-67 immunoreactivity in cancers is also attracting attention, as Ki-67 reflects cell proliferation, while p53 immunoreactivity is also of interest, as it reflects the malignancy of colorectal lesions. Accordingly, to determine these correlation, we investigated the distribution and intensity of COX-2, p53 and Ki-67 expression in both cancerous and non-cancerous tissues from patients with sporadic and ulcerative colitis (UC)-associated colorectal cancer. We selected 21 colorectal cancer specimens, obtained by surgical resection or colonoscopic biopsy, from 21 patients, including 3 with UC (13 men and 8 women; aged 42-78 years). Histological examination of hematoxylin and eosin-stained specimens revealed that 9 were well differentiated; 11. moderately differentiated: and 1 was a poorly differentiated adenocarcinoma. We used anti-COX-2, p53, and Ki-67 antisera to perform immunohistochemical staining by the labelled streptavidin biotin method and then assessed and graded the staining intensity and distribution. COX-2 staining was more intense in cancer tissue than in non-cancerous areas. Colorectal cancers associated with UC were not stained intensely. COX-2, p53, and Ki-67 positivity rates in were 38.1%, 38.1%, and 47.6%, respectively. There were no relationships among the distributions or intensities of COX-2, p53, and Ki-67 expression. Our results indicate that colorectal cancer tissues overexpress COX-2, but that there are no relationships between COX-2, p53, and Ki-67 expression, suggesting that COX-2 expression may not be related to cell proliferation or to the grade of malignancy. However, it is necessary to determine whether COX-2 in cancer tissue is involved in carcinogenesis or whether it is simply a product of cancer.
authors.affiliation: Second Department of Internal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sakuma
authors.forename: T
authors.initials: T
authors.lastname: Fujimori
authors.forename: K
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: A
authors.initials: A
authors.lastname: Terano
mesh_terms: D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000150:complications; D015179:Colorectal Neoplasms / Q000150:complications / Q000378:metabolism* / Q000648:ultrastructure; D051546:Cyclooxygenase 2; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000648:ultrastructure; D007527:Isoenzymes / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D007527:Isoenzymes; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases