Clinicopathological Implications Of VEGF/VEGFR-2 Expression And Microvessel Density In Soft Tissue Sarcoma

Objective: To research the expression of VEGF/VEGFR-2 and MVD in soft tissue sarcoma by immunohistochemistry,and analysis the correlation between them.In order to clear the correlation of VEGF and VEGFR-2expression with the clinical prognosis and overall survival.Methods: A retrospective analysis of 94 soft tissue sarcoma patients treated by operation in our hospital from 2005 to 2015.VEGF,VEGFR-2 and CD34 protein expression were analyzed by immunohistochemistry in 94paraffin-embedded tumor tissues of soft tissue sarcoma.Microvascular Vascular Density(MVD)was measured by counting vessels stained with CD34 antibody.The associations among VEGF/VEGFR-2 protein expression,MVD and prognosis were analyzed by statistical analyses.Results:1 Test object 94 cases,Among all the patients 51 were female and 43 were male,the median age was 50(rang 10-83)years.The soft tissue sarcomas comprised 94 tumors including fibrosarcoma(n=49),synovial sarcoma(n=21),liposarcoma(n=18)and undifferentiated pleomorphic sarcoma(n=6).The tumor origins were distributed as follows: 42.6% trunk,31.9% extremities,9.6% head/neck,4.3% visceral and 11.7% retroperitoneal.As shown in Table1,histological entity(P<0.001),malignancy grade(P=0.005),TNM stage(P=0.004),tumor depth(P=0.012)and metastasis at diagnosis(P=0.005)were all significant prognostic indicators for OS.2 There was no significant association identified between VEGF/VEGFR-2 expression levels or MVD for gender,tumor location,histological entity,tumor size,tumor depth or metastasis at diagnosis.High levels of VEGF protein expression were significantly correlated with the age of the patients(P=0.008),malignancy grade(P<0.001)and tumor nodemetastasis(TNM)stage(P=0.003).VEGFR-2 high expression were associated with malignancy grade(P<0.001)and TNM stage(P=0.010).While higher MVD was only correlated with the malignancy grade(P=0.004).3 VEGF protein expression were correlated with VEGFR-2 positively,the correlation coefficient was 0.652 and has statistical significance(P<0.001).The mean MVD of the high VEGFR-2 expression group was significantly greater than that of the low VEGFR-2 expression group(63 vs 41,P=0.007),while the mean MVD between the high and low VEGF protein expression groups was demonstrated no significant difference(53 vs 49,P=0.572).4 The expression of VEGF and VEGFR-2 in STS tissues were significantly correlated with OS via Kaplan-Meier analysis method(P=0.003,P=0.002).Multivariate analysis was also performed using the Cox proportional hazards model including Histological entity,Metastasis at diagnosis,Tumor depth,Malignancy grade,TNM stage,VEGF expression and VEGFR-2 expression.As the result presented,VEGF expression(P=0.018)correlates with STS prognosis and is a significant independent prognostic indicator of OS.5 The survival time of patients with soft tissue sarcomas showed significant differences with expression of VEGFR-2.The higher expression is,the shorter the survival time will be,which has statistical significance(P=0.003).And the survival time of high expression of VEGF was significantly lower than that of the low one(P=0.002).However,no significant difference was identified in the overall survival rate between the high and low MVD groups(P=0.375).Conclusion:1 VEGF expression correlates with STS prognosis and is a significant independent prognostic indicator of OS.2 VEGF protein expression were correlated with VEGFR-2 positively.3 The mean MVD of the high VEGFR-2 expression group was significantly greater than that of the low VEGFR-2 expression group,while the mean MVD between the high and low VEGF protein expression groupswas demonstrated no significant difference,These data implies that VEGF signaling through VEGFR-2 may play a role in leading endothelial cells proliferation and microvessel formation.4 There was no significant association identified between VEGF/VEGFR-2 expression levels for gender,tumor location,histological entity,tumor size,tumor depth or metastasis at diagnosis.High levels of VEGF protein expression were significantly correlated with the age of the patients,malignancy grade and tumor node metastasis(TNM)stage.VEGFR-2 high expression were associated with malignancy grade and TNM stage.5 The survival time of patients with soft tissue sarcomas showed significant differences with expression of VEGF and VEGFR-2,and the higher expression level of VEGF and VEGFR-2 is,the shorter the survival time of the patients will be.