The Distribution And Pilot Study On Mechanism Of Vasculogenic Mimicry In Carcinoid Tumour And Testicular Tumours

ObjectiveTo identify vasculogenic mimicry(VM) existence and indicate the clinical and pathological significance in Carcinoid tumor and Testicular tumors,and to investigate the role of Focal Adhesion Kinase(FAK),Matrix metalloproteinase(MMP2,MMP7,MMP9),CathepsinD(CathD),Integrinβ2 and Vascular endothelial growth factor(VEGF) in the formation of VM,to explain the potential mechanism of VM.Methods1.) Observe the distribution and clinical pathological significance of VM in Carcinoid tumor and Testicular tumors by PAS and CD34 double stainingFifty two carcinoid tumor cases and forty Testicular tumors cases undergoing surgery in Tianjin Medical University from 1^th/1,1992 to 20^th/12,2002 were collected in this study.The information of samples including age,gender,tumor location,size and metastasis were adequate.The VM's distribution and clinical pathological significance were observed.2.) Analyze the relation between VM and expression of FAK,Integrinβ2,CathD, MMPs and VEGFAfter constructing tissue microarray,VMD and MVD of these samples were evaluated.The expression of MMP2,MMP7,MMP9,CathD,Integrinβ2,FAK and VEGF were detected,whose difference of VMD and MVD were investigated between the positive and negative groups.The difference of these protein's expression were statistically analyzed.3.) Detect mRNA's expression of FAK,Integrinβ2,CathD,MMPs and VEGF by Real-time PCR(RT-PCR),analyzing the relation between them and VMFresh and refrigerant cases of Tissue Bank Department in Tianjin Medical University Cancer Hospital were collected from 2005 to now.Carcinoid tumour cases was 35 and Testicular tumours samples was 27.These protein's mRNA was observed by Real-time PCR,so that the mechanism of VM was analyzed from RNA.Results1.) The distribution and clinical pathological significance of VM in Carcinoid tumour and Testicular tumoursH＆E speciments were observed of 52 Carcinoid tumor's cases and 40 Testicular tumors's cases.By CD34＆PAS doubling staining the VM's structures were confirmed in them.It indicated that the presence of VM had a negative influence on prognosis between VM positive and negative groups,the P value is respectively 0.017 and 0.0127 in Carcinoid tumor and Testicular tumors.COX's proportional hazards model analysis indicated that the presence of VM was statistically significant in predicting survival of patients.2.) The expression of FAK,Integrinβ2,CathD,MMPs and VEGF by immunohis-tochemistry staining and the difference of VMD and MVDIn Carcinoid tumor tissue the expression of FAK,Integrinβ2 CathD and MMP2 is higher in VM positive group than the negative.However the expression of VEGF is reversed,P＜0.05;The VMD is higher in the positive groups of FAK,Integrinβ2, CathD,MMP2 than the negative,while VEGF is reversed;the MVD is higher in the positive of CathD,MMP2 and VEGF,P＜0.05;There was positive correlation between FAK and Integrinβ2,CathD and MMP2.The expression of FAK,CathD,MMP2 and MMP7 is higher in VM positive group than negative in Testicular tumors,P＜0.05;The VMD is higher in the positive group of FAK,CathD,MMP2 and MMP7;The MVD is higher in positive of FAK, CathD,MMP2,MMP7 and VEGF;There was positive correlation among FAK and CathD,CathD and MMP2,and CathD and MMP7.3.) The mRNA expression of relative genes by RT-PCRThe results of RT-PCR indicated that mRNA expression of FAK, Integrinβ2,CathD and MMP2 is higher in VM's positive group than negative,while VEGF is reversed in Carcinoid tumor,P＜0.05;the mRNA expression of FAK,CathD,MMP2 and MMP7 is higher in the positive than negative in Testicular tumors,P＜0.05.Conclusions1.) There was VM in Carcinoid tumor and Testicular tumors.The patients with VM differentiate poorly,metastasis earlier and had a poor prognosis.2.) In Carcinoid tumor tissue,FAK,Integrinβ2,CathD and MMP2 contribute to constructing the VM structure.FAK,Integrinβ2,CathD,MMP2 and VEGF contribute to building the vesseles of tumours.3.) In Testicular tumors tissue,FAK,CathD,MMP2 and MMP7 contribute to the formation of VM,while FAK,Integrinβ2,CathD,MMP2 and VEGF contribute to shaping the vesseles of tumours.