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Clinical Value and Expression of COX-2, MMP-9 and VEGF in Colorectal Cancer

Author: SongBaoLian
Tutor: ZhouYanBing
School: Qingdao University
Course: Surgery
Keywords: Colorectal cancer Invasion Metastasis VEGF COX-2 MMP-9
CLC: R735.3
Type: Master's thesis
Year: 2011
Downloads: 50
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Abstract


Background:Colorectal cancer is one of the most common malignant cancers, in the world, of which incidence and mortality is still on the rise. Although the clinic pathological stage is the golden criterion for the prognosis at present, the optimum prognostic criterion should be the combination of clinic-pathology and molecular markers. Unfortunately, there is none of molecular markers available for analysis of the malignant degree and prognosis. Since 80s, large-scale epidemic research had shown that colorectal cancer disease rate in people who take NSAIDs is 40 %-50% less than others are. Researches after that also showed NSAIDs could reduce occurrence of oesophagus and stomach cancer, and the possible mechanism to its inhibition on COX-2 and VEGF, which were key cytokines in tumor occurrence and metastasis, and important prognostic factors, Extracellular stroma is very informant in restraining the carcinoma invasion and metastasis, and MMP-9 is the key enzyme in catabolism of extracellular stroma. TNM classification is not suitable for clillical prognostic evaluation. Along with the progress of colorectal cancer molecular biology and the molecule immunology study, people is trying to seek more effective forecast index to the patient make inroads on the metastasis and the prognosis carrying out a forecastObjective:To study the clinical values of expression of COX-2, MMP-9 and VEGF in colorectal cancer tissue.Methods and Results:Part I Expressions of VEGF, COX-2 and MMP-9 in normal tissues, beside-tumor tissues and tumor tissues.Methods Immunohistochemistry stain of VEGF, COX-2, and MMP-9 of 30 samples of normal tissues and beside-tumor tissues and tumor tissues, all the samples were taken from the same patient.Result:1. No expression of VEGF, COX-2 and MMP-9 were in normal tissues, in contrast to low expression of VEGF, COX-2 and MMP-9 in beside-tumor.2. In 80 colorectal cancer samples, the expression rate of VEGF, COX-2 and MMP-9 were 75.0%(60),70.0%(56) and 65.0%(52) respectively.3. In 30 beside-tumor tissues samples, the expression rate of VEGF, COX-2 and MMP-9 were 20.0%(6),23.3%(7) and 20.0%(6) samples respectively.4. P of normal tissues VS colorectal cancer (<0.01), normal tissues VS beside-tumor tissues (<0.05), and colorectal cancer VS beside-tumor tissues (<0.05), were all of statistical significance. Conclusion:VEGF, COX-2 and MMP-9 express negative in the normal tissue, low express in the beside-tumor tissue, high express in colorectal cancer tissue, indicated that VEGF, COX-2 and MMP-9 examination is feasible and believable.Part II The relationship between the quantity of VEGF, COX-2, MMP-9 and clinical examinationsMethod:80 cases of colorectal cancer patients. Clinical data included sex, age, tumor diameter, differential degree, invasion degree, TNM stage, lymph node metastasis and liver metastasis was recorded for analysis. All tumor slices were immunohistochemistry stained for VEGF, COX-2 and MMP-9 expression exam. Result data was statistical analyzed with SPSS 13.0 for Chi-square test.Results:80 cases of colorectal cancer patients1. In 41 male cases, VEGF, COX-2 and MMP-9 expresses positive in, the 32,30and 30 cases respectively; In 39 Female cases, the VEGF, COX-2 and MMP-9 expresses positive in 28,26 and 22 cases respectively.2. Age<60 was 327cases, the VEGF, COX-2 and MMP-9 positive cases were 25,25 and 24 respectively. Age≥60 was 43 cases, the VEGF, COX-2 and MMP-9 positive cases were percent 35,31 and 28 respectively.3. Diameter<5cm 39 cases, the VEGF, COX-2 and MMP-9 positive cases were 27,28 and 23 respectively, diameter>5cm 41 cases, the VEGF, COX-2 and MMP-9 positive cases were 33,28 and 29 respectively.4. Liver metastasis was 46 cases, the VEGF, COX-2 and MMP-9 positive cases were 45, 43 and 40 respectively; no liver metastasis 34 cases, the VEGF, COX-2 and MMP-9 positive cases were 15,13 and 12 respectively.5. High polarization 32 cases, positive cases were 14,12 and 14 respectively; middle-low polarization 48 cases, positive cases were 46,44 and 40 respectively.6. Invaded depth reach to muscle layer 30 cases, positive cases were 12, Hand 11 respectively. Chorion layer and Ex-chorion 50 cases, positive cases were 48,45 and 41 respectively.7. According to the guideline of UICC2002,342 cases were stage I, positive cases were 14,13 and 12 respectively, stage III-IV 48 cases, and positive cases were 46,43 and 40 respectively.8. Patients without lymph metastasis 33 cases, positive cases were 15,12 and 214 respectively; Patients with lymph metastasis 47 cases, positive cases were 45,44 and 40 respectively.9. Colon carcinoma 42 cases, positive cases were 30,23 and 26 respectively. Rectal cancer 38 cases, positive cases were 30,23 and 26 respectively.Conclusion:Invasion degree, differentiation degree, TNM staged, lymph node metastasis and liver metastasis significantly relate to over-expression of VEGF, COX-2 and MMP-9.PartⅢThe relativity of VEGF, COX-2 and MMP-9 in the invasion and metastasis of colorectal cancer.Method:Expression of VEGF, COX-2 and MMP-9 were examined in 80 colorectal cancer tissues. Result data was statistical analyzed by SPSS 13.0 for Chi-square test.Results:In 80 cases, COX-2 (+) and VEGF (+) 48 cases,60.0%; COX-2 (+) and VEGF (-) 8 cases,10.0%; COX-2 (-) and VEGF (+) 12 cases,15.0%; COX-2 (-) and VEGF (-) 12 cases,15.0%; COX-2 (+) and MMP-9 (+) 42 cases,52.2%; COX-2 (+) and MMP-9 (-) 14 cases,17.5%; COX-2 (-) and MMP-9 (+) 10 cases,12.5%; COX-2 (-) and MMP-9 (-) 14 cases,17.5%. VEGF (+) and MMP-9 (+) 50 cases,62.5%, VEGF (+) and MMP-9 (-) 510 cases,12.5%. VEGF (-) and MMP-9 (+) 2cases,2.5%, VEGF (-) and MMP-9 (-) 18 cases 22.5%.Conclusions:VEGF, COX-2 and MMP-9 had positive relativity in the invasion and metastasis of colorectal cancer.Conclusions1. The expression of VEGF, COX-2 and MMP-9 was negative in the normal tissue, low expression in the beside-tumor tissue, high expression in colorectal cancer tissue.2. The expressions of VEGF, COX-2 and MMP-9 was related with TNM staging, lymph node metastasis and liver metastasis have significance to the expression of VEGF, COX-2 and MMP-9.While sex,age,tumor’s position and diameter. Results showed that VEGF, COX-2 and MMP-9 have something with the invading and metastasis of rectum carcinoma, which can be inspecting guideline.3. VEGF, COX-2 and MMP-9 have positive relativity in the invading and metastasis of colorectal cancer, and COX-2 over-expression can accelerate the expression of VEGF and MMP-9.

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