Expression Of Cyclooxygenase-2, Vascular Endothelial Growth Factor-c And Cd44v6 In Esophageal Squamous Cell Carcinoma Tissue

Background and ObjectivesTHE China is one of country where the esophageal carcinoma is in higher morbidity,the 5-year survival rate of postoperative cases is about 20%,and accounting for 60%of all over the world,which is a serious threat to human health.In China,95%of esophageal cases are esophageal squamous cell carcinoma(ESCC), which are the research priority of esophageal carcinoma.The major reasons of treatment failure and death are invasion and metastasis,angiogenesis and lymphangiogenesis play a key role in the pathogenesis.Lymphatic metastasis is not only the most common spread pathway of most malignant epithelium tumor,but also a major factor affecting recurrence and prognosis.Lymph vessel hyperplasia and expansion are often found in tumor stroma with lymph node metastasis.Cyelooxygenase-2(COX-2) overexpresses throughout the entire process of genesis and development.It may promote the generation and metastasis of cancer in various ways,playing an important roles in tumor angiogenesis and lymphangio -genesis.Vascular endothelial growth factor-C(VEGF-C) is the main factor to promote lymphatic vessel formation and is highly expressed in a variety of tumor tissue.Binding with vascular endothelial growth factor receptor-3(VEGFR-3), VEGF-C exclusively stimulates epithelial proliferation,and induces lymphangio -genesis and Iymphatic vessel expansion,thereby promoting tumor microlymphatic generation.Some reports linked the high expression of CD44v6 to tumor progression in recent years,however,its machanism is not clear.In this thesis,we studies expression of COX-2,VECF-C and CD44v6 in esophageal squamous cell carcinoma.To understand the clinic significance, expressions of COX-2,VEGF-C and CD44v6.were detected in ESCC and analyzed with their clinicopathological Parameters.Meanwhile,we investigated whether their expression predicts response to prognosis.Materials and Methods1.A total of 58 cases from Paraffin-embedded specimens at the Henan Province Tumor Hospital from 2002 to 2003,and confirmed pathologieal diagnosis of ESCC.20 cases of normal esophageal tissue were chosen as contrast group, which were obtained from patients with ESCC 5 cm far from tumor tissue and confirmed histologieally.Any chemotherapy and radiotherapy have never been carried out in all cases before operation or diagnosis.2.The expression of COX-2,VEGF-C and CD44v6 was detected by immunohistochemical staining SP method.Combining with the clinicopath -ological features,the author analyzes their clinical significance and the function in prognosis.We have the whole follow-up data.And the follow-up time ranging from 9 to 65 months.and the cut-off time of follow-up was 1,May,2008.3.Statistical analysis:The data were analyzed by SPSS 13.0.Fisher's exact test of probabilities,Chi-square test,COX's proportional hazard regression model and Spearman rank-correlation test were used to analyze the date,The survival curve was obtained with Kaplan-meier test.Results1.Expression of COX-2 in ESCC was higher than control group(70.6%vs10%, P＜0.01),and was not related with expression of lymphnodemetastasis,clinical stage,turnor differentiation(P＞0.05).and was negative correlated with overall survival time.The positive staining product is brown granules,mainly loealized in cytoplasm of cancer cells.2.Expression of VEGF-C in ESCC was higher than control group(53.4%vs0%, P＜0.01),and was positively and remarkably related with expression of lymph node metastasis(P＜0.01),but negatively with turmor differentiation(P＜0.01),and VEGF-C was not correlated with overall survival time.The positive staining product is brown granules,mainly loealized in cytoplasm of lylnphatic endothelial cells or cancer cells.3.Expression of CD44v6 in ESCC was higher than control group(65.5%vs0%, P＜0.01),and was positively related with expression of lymphnodemetastasis (P＜0.05),but negatively with turnor differentiation(P＜0.05),and CD44v6 was not correlated with overall survival time.The positive staining product is brown granules,mainly loealized in cytoplasm of cancer cells.4.COX-2 expression was significantly positive relation with VEGF-C(rs=0.221, P=0.018＜0.05).But CD44v6 was not correlated with COX-2 or VEGF-C (rs=0.025,0.095;P=0.458,0.358).It was no statistically significant association between results of combined detection of COX-2,VEGF-C,CD44v6 and overall survival time.Conclusion1.COX-2,VEGF-C and CD44v6 Play key roles in the development,invasion and metastasis of ESCC,and may be important indieators of treatment and prognosis.2.VEGF-C and CD44v6 are a key factor of lymphantic node metastasis in ESCC. and may be an important indicator of monitoring of tumor cells and its prognostic.3.COX-2 may promote lymphangiogenesis and lead to tumor invasion and lymph node metastasis by upregulating VEGF-C expression in ESCC.