The Study Of Clinical Significance And Related Mechnism On Vasculogenic Mimicry In Prostate Cancer

Objective:The experiment is intended to expore if a unique blood mode-vasculogenic mimicry(VM) exist in prostate cancer and further to observe its morphology and distribution,to analyze the relationship between prognosis and VM from clinical date,follow-up date and prognostic date.To investigate the potential mechanismofVM, and the role MMP-2 (Matrixmetalloproteinase-2)played in the formation of VM.Methods:To collect 96 prostate cancer resection samples by radical prostatectomy from January 1 1995 to December 31 2008 of the Second Hospital of Tianjin Medical University. Immunohistochemical staining of CD31 (Platelet-endothelial cell adhesion molecule-1)and PAS(Periodic acid-sciff) special histochemical staining were conducted to explore if VM exist in prostate cancer,and its morphology and distribution in prostate cancer.Further to observe the different expression of MMP-2 in VM positive and VM negative tissue,and to explore the effect of tumor cells in the formation of VM by secreting MMP-2.To collect the clinical data(ages,examination results,treatment and so on),follow-up date(the level of prostate specific antigen,results of digital rectal examination imaging findings and so on),prognostic date(metastasis,recurrence,die), and to analyze the relationship between disease progression and VM based on the above dates,and the clinical significance of VM.Results:From immunohistochemical staining of CD31 and and PAS special histochemical staining,we observed 24 cases of VM circuled by tumor cells in the total 96 cases, within which red blood cells can be seen.The boundary membrane of VM is PAS positive,which can be continuous or incontinuous.Different from endothelial cells,the tumor cells do not secret CD31.It is also observed that VM exist in the cancer of high gleason grade,which are the low differentiated carcinoma,and the level of TPSA is higher in the VM positive patients.The existence of VM has a signifcant relationship with the prognosis of the patients,which is that the VM positive patients have more poor prognosis than the negative ones.It is found that the tumor cells secret much MMP-2 from immunohistochemical staining of MMP-2,and its density has a significant relationship with the expression of VM.The density of VM positive ones is higher than the VM negative ones,and it has a statistic difference.It is analyzed there is a close relationship between MMP-2 and the formation of VM.Conclusions:It is confirmed that VM do exist in the prostate cancer as an independent structure through our study,and it is more common in the cancer of high gleason grade.The tumor cells form a channal(VM)pumping blood through its self-deformation and interaction with ECM,to supply the rapidly growing tumor tissue.For its unique morphology and structure,tumor cells contact with the blood directly,so it is more easy for the metastasis,and the progression-free survival of VM positive ones is worse than the negative ones.It can be the reason why some patients have a poor treatment efficiency and prognosis.The formation of VM has a unique molecular mechnasim.Tumor cells secreting MMP-2 to degrade the ECM to provide space for the VM,and remodel the ECM at the same time to form VM to supply the tumor growth.To sum up,MMP-2 and VM can be the indicators of poor prognosis,and can be the new target for the treatment of prostate cancer.