Localization of cyclooxygenase-2 in human recurrent colorectal cancer

Aim: The aim of this paper is to examine COX-2 expression in human recurrent colorectal carcinoma tissues using immunohistochemistry and quantative real-time PCR (qPCR). Methods: Colon and rectal specimens were obtained from 26 patients with recurrent colorectal carcinomas. We examined COX-2 expression in human recurrent colorectal carcinoma tissues using immunohistochemistry and quantative real-time PCR (qPCR). Results: In recurrent colorectal cancer a strong cytoplasmic and perinuclear staining of COX-2 was found. Moderate to strong immunosignals were detected in almost all of the carcinomas. We observed a strong specific staining of COX-2 in vascular endothelium. COX-2 immunoreactivity was also detected in stromal cells such as mononuclear cells, fibroblasts, and smooth muscle cells. The real-time PCR analyses demonstrated marked overexpression of the COX-2 gene in the cancer mucosa in concert with the immunohistochemistry data. Conclusion: We investigated COX-2 expression at the level of its protein as well as its messenger RNA in a series of recurrent colorectal cancers. These observations give additional information about the possibility that COX-2 could be involved in tumor promotion during colorectal cancer progression. Colorectal cancer is still an important cause of death, although the incidence and mortality rates are decreasing.1 An important explanation for the unfavorable prognosis of colorectal cancer patients is the fact that cancer recurs in about 40% of patients.2 Most tumors recur in the first two years following surgical resection and in many cases is ultimate cause of death. During the past several years many studies have been conducted to determine the precise role of eicosanoids in colorectal carcinogenesis. Cyclooxygenase (COX) is a key enzyme in the production of the prostaglandins (PG) and other eicosanoids. These products may have multiple roles in modulating cell growth and immunosurveillance in cancer.3,4 Two COX isoenzymes have been identified.5 COX-1 is constitutively expressed, while COX-2 is inducible in a number of cell types by a variety of factors such as cytokines, growth factors, oncogenes and tumor promoter.6,7 COX-2 is undetectable in normal intestine and its levels are elevated in up to 85% of colorectal adenocarcinomas.8 Experimental knockout of COX-2 ORIGINAL RESEARCH © 2010 CIM Clin Invest Med • Vol 33, no 1, February 2010 E22. results in suppression of intestinal polyposis in animal models of familial adenomatous polyposis.9 Epidemiological studies have shown lower than expected rates of colorectal adenomas and carcinomas in subjects who have taken non-steroidal antiinflammatory drugs (NSAIDs).10-14 This cancer chemopreventive effect has been confirmed by animal models of colon and skin cancer for both conventional NSAIDs15-19 as well as for selective COX-2 inhibitors.20-22 Although the precise mechanism for the protective effects of NSAIDs are still unknown, the ability of these drugs to induce cell cycle arrest and apoptosis has received much attention. Here, we examined COX-2 expression in human recurrent colorectal carcinoma tissues using immunohistochemistry and quantative real-time PCR (qPCR). We speculate that COX-2 overexpression in colorectal recurrences could provide a rational basis for studying chemoprevention of advanced disease with the use of selective COX-2 inhibitors after surgical curative resection. Materials and Methods