Study On The Relationship Between VEGF-C And VEGF-D With Lymphatic Metastasis In Non-small Cell Lung Cancer

Background:Metastasis is a fundamental feature of malignancy.Lymphatic metastasis is a significant path for cancer.Lymph nodes metastasis is an important prognostic indicator in patients with cancer.Along with lymph vessel growth factor VEGF-C, VEGF-D and lymph vessel endothelial cell marker D2-40 were discovered and widespread applied in animal experiment and clinical study,the role had been acknowledged in cancer lymph vessel growth and metastasis.The study is much between VEGF-C with cancer,and it is less between VEGF-D with cancer in the world,the results are not same.In domestic,the study on VEGF-C in NSCLC is less, and the study on VEGF-D in NSCLC is not found.Objective:Through detecting the expressive levels of VEGF-C and VEGF-D in NSCLC, to analyse the characteristics of expression and the correlation with its clinicopathological factors,to investigate the possible mechanism of lymphangiogenesis and lymph node metastasis in NSCLC,to provide some theory for NSCLC in predication of prognosis and treatment.Methods:The expression of VEGF-C,VEGF-D and D2-40 were detected in 62 paraffin sections of NSCLC and 10 normal lung tissues near the cancer by immunohistochemistry method.Assessments of lymphatic vessel density(LVD)and positive rates of VEGF-C and VEGF-D were performed and their relationship were analysed.Results:1.LVD in the NSCLC group was significantly higher than that in the normal lung tissues group(P=0.000),LVD in the positive lymph node metastasis group was significantly higher than that in the negative lymph node metastasis group(P=0.006). Positive correlation was found between LVD with lymph node metastasis zone(r=0. 379,P=0.002).2.The positive rate of VEGF-C in the NSCLC group was significantly higher than that in the normal lung tissues group(P=0.000).No correlation were found between the positive rate of VEGF-C with age,gender,and histological type(P=0.053,0.385, 0.117).The correlation were found between the positive rate of VEGF-C with tumor diameter and lymph node metastasis(P=0.025,0.003).The positive rate of VEGF-C was correlated with TNM stage in NSCLC(P=0.000).LVD in the positive VEGF-C group were significantly higher than that in the negative VEGF-C group(P=O.001). Positive correlation was found between the expression of VEGF-C with LVD(r=0. 312,P=0.014).3.The positive rate of VEGF-D in the NSCLC group was significantly higher than that in the normal lung tissues group(P=0.000).No correlation were found between the positive rate of VEGF-D with age,gender,histological type,and tumor diameter (P=0.713,0.897,0.267,0.284).The positive rate of VEGF-D in the positive lymph node group was significantly higher than that in the negative lymph node metastasis group(P=0.005).The positive rate of VEGF-D was correlated with TNM stage in NSCLC(P=0.000).LVD in the positive VEGF-D group was significantly higher than that in the negative VEGF-D group(P=0.000).Positive correlation was found between the expression of VEGF-D with LVD(r=0.437,P=0.000).Conclusion:Lymphangiogenesis is a significant factor for tumor lymphatic metastasis, VEGF-C and VEGF-D may mediate lymphatic metastasis of NSCLC by the way of inducing lymphangiogenesis,and may serve as prognostic indicators and guide the treatment.