Research On The Expression And Clinical Significance Of Cyclooxygenase-2 In Wilms' Tumor In Children

Background and objective: The incidence of malignant tumors has increased gradually, which becomes the second causation of children death now. Of all abdominal malignant tumors of children, the incidence of Wilms'tumor(WT) is highest. The survival rate without tumor recurrence has been increased obviously with the improvement of therapeutic measures, however, the prognosis of some patients in stageâ…¢toâ…¤is very poor because of the metastasis of the tumor cells. Although many researchs have been executed to detect the mechanisms of nephroblastoma invasion, no characteristic marker has been found to evaluate the prognosis and act as target of therapyRecently, over-expression of cyclooxygenase (COX-2) has been demonstrated in several carcinomas such as colon carcinoma, lung cancer , breast cancer , prostatic carcinoma, and so on, which promotes proliferation and invasion of tumor, and the proliferation of tumor could be disturbed by cox-2 inhibitor. Lee A et al[1] reported that the inducible enzyme cyclooxygenase-2(COX-2) acted as an important role in tumor angiogenesis. SC-236, which was one of the COX-2 inhibitors, caused defective vascular assembly, and impaired endothelial survival and tumor growth significantly. Because the over-expression of COX-2 is related to the proliferation of WT cells, we design this study to detect the expression of cox-2 in WT of childen, and evaluate the relations among the stage of clinical classification, pathohistology type , pre-operative chemotherapy and prognonasis, and prove whether the pre-operative chemotherapy will disturb its expression and it could act as one of characteristic markers of tumor to evaluate the prognosis .Methods: 1. collecting and analyzing 33 clinical cases of WT patients with VCR and ATCD chemotherapy in Children Hospotial, Chongqing Medical University from January 2000 to December 2004, and following up over 2 years. The gender: 24 boys and 9 girls; The age : from 2 months to 8 months over 7 years old, mean age: 6 months over 2 years. Nearside is 14 examples, RT is 17 examples, both sides are 2 examples; Pre-operative chemotherapy group is 15 examples including 6 examples stageâ…¡, 4 examples stageâ…¢, 3 examples stageâ…£, and 2 examples stageâ…¤; Without pre-operative chemotherapy group is 18 examples including 5 examples stageâ… , 5 examples stageâ…¡, 6 examples stageâ…¢and 2 examples stageâ…£. Pathohistology type : 18 examples are stromal elements, 6 examples are blastemal elements, 9 examples are epithelial components. 2. Collecting paraffin samples of WT and slicing , making a definite diagnosis by HE staining ,using anti-cox-2 polyclonal antibody to detect the expression level of cox-2 in 33 examples . To detect the expression of cox-2 in WT paraffin samples by immunohistochemical method with colonal carcinoma paraffin samples as positive control and PBS as negative control, and analyze its over-expression with relations to the stage of clinical classification, pathohistology type , pre-operative chemotherapy and prognonasis.Results: 1. In our study, 33 examples are alive, 7 examples were dead , 2 years survival rate is 78.8%(26/33), the positive expression rate of cox-2 is 54.5%(18/33), including stageâ… 40%(2/5), stageâ…¡63.6%(7/11), stageâ…¢40%(4/10), stageâ…£80%(4/5), stageâ…¤50%(1/2),respectively. 2. The positive expression rate of cox-2 in every pathohistology type : stromal elements 66.7%(12/18), blastemal elements 50%(3/6), epithelial elements 33.3%(3/9)respectively. 3. The positive expression rate of cox-2 by pre-operative chemotherapy is 60%, without pre-operative chemotherapy is 50%, and there is not significant correlation between pre-operative chemotherapy group and without pre-operative chemotherapy group (p>0.05). 4. The positive expression rate of cox-2 in survival group is 42.3%(11/26), dead group is 100%, which shows that there is significant correlation between survival group and dead group (p<0.05). Our study shows that the over-expression of cox-2 in pediatric WT maybe have more risk of recurrence and metastasis and poor prognosis. Conclusions: In our study, the over-expression of cox-2 in WT has been detected in some patients, and the positive expression rate of cox-2 is 54.5%. Although the positive expression rate is different in each pathohistology types , including stromal elements is 66.7%, blastemal elements is 50%, epithelial elements is 33.3% ,respectively, the positive expression rate of cox-2 isn't related to the stage of clinical classification. Without significant correlation between pre-operative chemotherapy group and without pre-operative chemotherapy group which shows that chemotherapy doesn't disturb the expression of cox-2 in WT. The different positive expression rate of cox-2 with significant correlation between survival group and dead group shows that detecting cox-2 expression in WT will act as one of the characteristic markers of tumor to evaluate the prognosis and over-expression of cox-2 in pediatric WT maybe have more risk of recurrence and metastasis and have poor prognosis. So the selection of treatment maybe be careful and decrease the risk of recurrence by effective intervention study to improve cure rate , and our study maybe act as significant role for exploring new treatment of WT.