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The Clinical Significant Of COX-2 Expression In Colorectal Tumors

Posted on:2004-09-11Degree:MasterType:Thesis
Country:ChinaCandidate:S Y PanFull Text:PDF
GTID:2144360092490712Subject:Oncology
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Epidemiological studies have shown a lower mortality of colorectal adenomas and carcinomas in population with nonsteroid anti-inflammatory drugs ( NSAIDs). It was suggested that cyclooxygenase (COX) play a pathogenic role in colonic tumorigenesis. Disruption of COX-2 gene or the selective COX-2 inhibition in the mouse model of polyposis coli dramatically reduces polyp growth. COX-2 is a rate-limiting enzyme in prostaglandins (PGs) synthesis and the prostaglandin endoperoxide synthase 2(PGE2) counted for major of PGs inhibits both the activation of NK, LAK cell, Cytotoxic cell and the expression of receptors of IL-2 and IFN-r. In the patients with familial adenoma polyposis, sulindac administration resulted in a striking reduction in the size and number of adenomas.Recently, the relationship between the expression of COX-2 and differentiation of the tumor has been reported. Homogeneity expression of COX-2 in poor differentiation colorectal carcinomas and heterogeneity expression in well differentiation colorectal carcinomas was noticed. In this the expression of COX-2 of colorectal adenomas and carcinomas were studied to investigate its relationships with other biological characteristics of colorectal carcinomas.METNOD:One hundred seventeen patients (53% male, mean age 56.50 years old) with colorectal tumor diagnosed between 1999 and 2002 in the Second Affiliate Hospital Zhejiang University College of Medicine were included in this study. The tumors were 21 adenoma and 96 carcinomas. The clinical stage of carcinomaswere TNM I 19 cases, II23, III38and IV 16. 42.7% of the carcinomas were lymph node involvement and 13.7% were other organs involvement .All patients underwent surgical resection of their tumors. Other 13 normal colonic tissues were also studied.Immunohistochemical staining was performed in the study with Vltra Sensitive SP kit. The specimens were embedded in paraffin and serially sectionedonto microscope slides at a thickness of 4 μ m. The slides were deparaffinizedand managed with EDTA, endogenous peroxidase blocking solution, normal nonimmunone serum, primary antibody against human COX-2, biotin-conjugated second antibody; streptavidin-peroxidase, DAB (a peroxidase substrate solution) respectively. Positive staining was indicated as brown-black deposits. For each tissue specimen, the extent and intensity of staining with COX-2 antibodies was graded on a scale of (-)+++ by two blinded observers on two separate occasions using coded sliders and an average score was calculated. A (+++) implies that all staining was maximally intense throughout the specimen, while (-) implies that staining was absent throughout the specimen. The locations of staining were also recorded. The data were analyzed with the software of SPSS 10.0. Klendall t-b correlation analysis was used to find the correlation between the expression of COX-2 and clinical pathological features and the data of every group were tested by X2 test.RESULT:Marked expression of COX-2 was found in cancer cells, inflammatory mononuclear cells, vascular endothelial cells and fibroblasts. The extent and intensity of the COX-2 in cancer cells was greater than others. COX-2 was very weak or negative in normal colorectal tissue surrounding the tumor. 95% of the colorectal carcinomas and 43% of the colorectal adenomas were positive of COX-2. The relationships between COX-2 expression and various clinical and pathological features were studied and the results suggested (1) COX-2 immunostaining was significantly more extensive and intense in colorectalcarcinoma cells than in adenomas or normal colorectal epithelial cells (p<0.01), (2) There was significant difference between the maximum tumor diameters≥5cm and <5cm(p<0.01), (3) The extent of COX-2 staining was greater in more advanced TNM stage tumors(p<0.01), (4) There was significant difference between the patients with lymph node involvement and no lymph node involvement (p<0.01), (5) There was significant difference between the patients with other organs involveme...
Keywords/Search Tags:Significant
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