Investigation Of Molecular Mechanism Of Vasculogenic Mimicry In Malignant Tumor From Muscle

Aims:To observe and identify VM existence in malignant tumor from muscle,and indicate the clinical and pathological significance of VM through a retrospective study with human samples.Based on these,we will to investigate the role of VM and the molecular mechanism involving in VM formation.Methods:1.Forty-five leiomyosarcoma cases and forty-six rhabdomyosarcoma cases undergoing surgery in Tianjin Medical University from 1^th/1,1982 to 30^th/12,2002 were collected in this study.The clinicopathologic information of samples is complete. HE staining and CD34/PAS immunohistochemical double staining were performed to observe the existence and distribution of VM,and to explore the clinicopathologic significance of VM and the relationship between prognosis and VM.2.Tissue microarray and immunohistochemical staining were applied to detect the expression of FAK,cathD and MMP-2.Staining index(SI) was assessed to investigate the different expression between VM-positive group and VM-negative group,and to study the relationship between them and VM.3.Bwteen January 2006 and December 2008,twenty leiomyosarcoma cases and thirty rhabdomyosarcoma cases with fresh tissue were collected from Tianjin Medical University.Real-time PCR was applied to detect the mRNA expression of FAK, CathD and MMP-2,and to investigate the different expression between VM-positive group and VM-negative group.Results:1.VM exists in human leiomyosarcoma and rhabdomyosarcoma.In HE staining slides,there were VM,formed by tumor cells but not endothelial cells,in which red blood cells presented;near these structures,there were no hemorrhage,necrosis and inflammatory cells infiltratin.In CD34/PAS double staining slides,VM was tumor cells formed channel with CD34-negative,there was PAS-positive material separate tumor cells and red cells.2.Statistical results showed that 55.6%(25/45) of leiomyosarcoma had VM,and 56.5%(26/46) of rhabdomyosarcoma had VM.VM is close-related with tumor sizes, metastasis and survival status(P＜0.05),however,unrelated with the age and gender of patient,location and recurrence.Kaplan-Meier survival analysis indicated that the prognosis of patients with VM was worse than the prognosis of those without VM (P＜0.05).3.IHC results shows that the expressions of FAK,CathD and MMP-2 in VM-positive group were statistically significant higher compared with those in VM-negative group.The expression of FAK is close-related with the expression of MMP-2 in rhabdomyosarcoma and leiomyosarcoma.4.Real-time PCR results showed that the mRNA expressions of FAK,CathD and MMP-2 in VM-positive group were statistically significant higher compared with those in VM-negative group in leiomyosarcoma and rhabdomyosarcoma.Conclusion:1.VM exists in malignant tumor from muscle.Under appropriate matrix microenvironment conditions,remodeling of the extracellular matrix(ECM) and the connection of the VM channel and host blood vessels to acquire a blood supply from the host tissue.2.VM is close-related with tumor sizes,metastasis and survival status.Tumors with VM are likely to spread via blood vessels in the early stage,and the patients faced an inefficient curative effect and a poor prognosis.3.FAK,CathD and MMP-2 expressed higher in VM-positive group than VM-negative group.This shows that the three molecules may participate in VM formation by degradating base-membrane and extracellular matrix in malignant tumor from muscle.4.The expression of FAK was closely correlated to the expression of MMP-2.This shows that can enhance invasion and metastasis ability of tumor cells and contribute to the formation of VM together.