Clinical Study Of Vasculogenic Mimicry In Colorectal Carcinoma

Objective: To investigate if vasculogenic mimicry (VM) exists in colorectal carcinoma and further to explore its potential molecular mechanism to explain the clinical significance of VM .Methods: To collect 102 colorectal carcinoma resection samples with their clinicopathologic data. Immunohistochemical staining of CD31, CD105, VEGF and PAS special histochemical staining were conducted to observe if VM exists in colorectal carcinoma. The correlation of pathological exzamination and clin -ical oucomes were analyzed to understand the biological behavior between VM group and non-VM group. Immunohistochemical staining of MMP-2 and VEGF to explore its molecular mecha -nism evaluated by a scoring method reported by Mattern et al.Results:1 VM exist in colorectal cancer .VM were seen in 11 cases of 102 colorectal carcinama specimens through CD31 double staining with PAS, HE staining . And then conducted 11 cases of specimens CD105, CD31, VEGF staining to further confirm the existence of VM. The observed evidence of VM through histolog and immuno -histochemical analysis of colorectal carcinoma are as follows: 1.1 CD31 and CD105 did not stain the cells that outlined these pathologic solid tubular structures(VM),which prove these cells are not endothelial cells1.2 red blood cells exist in the lumen of these pathologic solid tubular structures(VM) instead of necrosis of the tumor cells and inflammatory cells in the central region of tumor cells nest .2 The biological behavior of VM2.1 The relationship between pathologic classification of colorectal carcinoma and VM :3.33% (1/30) exhibited VM of well- differentiated adenocarcinoma ;4.17% (1/24) exhibited VM of moderate-differentiated adenocarcinoma ;18.75%(9/48) exhibited VM of poor-differentiated adenocarcinoma. To compare poor-differentiated adenocarcinoma with well-differentiated adenocarcinoma and moderate-differentiated adenocarcinoma , the poor- differentiated adenocarcinoma exhibited more VM specimens than well-differentiated adenocarcinoma and moderate-differentiated adenocarcinoma, there are significant difference between them (P <0.05).2.2 Reforming Dukes classification of 102 colorectal carcinoma and VM: We adopt Dukes classification to evaluate the biological behavior of VM. The Dukes classification stage of VM group was more advanced than that of the non-VM group.There are statistically significant difference (P <0.05). But at the same time we compared the hematogenous metastases between the two groups , we found that VM group had a higher rate of occurrrence of hematogenous metastsses(P<0.05)than the non-VM group. 2.3 MVD of 102 colorectal carcinoma and VM: MVD in VM group are lower than that in non-VM group and the difference is statistically significant(P<0.05), which means expression of MVD is not in accordance with the malignancy of colorectal carcinoma.3 The primary investigation of the mechanism of VM in colorectal carcinoma3.1 VEGF expression in VM group and non-VM group: VEGF express mainly in the cytoplasm. But we can also see the positive staining on the membrane. In colorectal carcinoma, the main positive expression of VEGF were observed in tumor cells as well as some stromal vascular endothelial cells.VEGF expression in some tumor tissue was certain homogeneity, while in some other tumor heterogeneity . The staining of cancer marginal clearly enhanced. VEGF is known as the strongest angiogenesis-induced factor in tumor angiogenesis, which can induce blood vessel formation and enhance the role of vascular permeability. 63.73% (65/102)colorectal carcinoma soecimens express VEGF.The positive expression rate of VEGF of the VM group was 45.45% (5/11), the positive of VEGF of the non-VM group was 65.93% (60/91). The cells outlined these pathologic solid tubular structures(VM) can express VEGF protein and demonstrate an endothelial phenotype, which suggest these cells plasticity.We select a scoring method reported by Mattern et al to compare the difference of VEGF expression between the two groups ,there are no significant difference between them(P>0.05) . 3.3 MMP-2 expression in VM group and non-VM group: MMP-2 express mainly in the cytoplasm.But we can also see the positive staining on the membrane. In colorectal carcinoma, the main positive expression of MMP-2 was observed in tumor cells as well as some stromal cells. MMP-2 staining of the marginal in some tumor tissue clearly enhanced. 54.90%(56/102)colorectal carcinoma specimens express MMP-2.The positive expression rate of MMP-2 of the VM Group was 63.64%(7/11).The positive expression rate of MMP-2 of the non-VM group was 49.45%(45/91).We compared the difference of MMP-2 Expression between the two groups by Mattern scoring . Statistical analysis showed that MMP-2 has a more intense expression in the VM group than the non-VM group(P<0.05).Conclusion:1 Vasculogenic mimicry exists in colorectal carcinoma. It is possible that the tumor cells adapt to the environment and acquire blood supply to sustain growth and metastasize by his special blood supplying mode.2 PAS positive basement membrane material may not be necessary for the vasculogenic mimicry. Not all vasculogenic mimicry has PAS positive basement membrane.3 Expression of VM in colorectal carcinoma correlates with the malignent biological behavior of colorectal carcinoma.High invasive colorectal carcinoma are more easy to form VM than the poor invasive colorectal carcinoma.4 In the colorectal carcinoma patients belonging to VM group had a higher rate of occurrence of hematogenous metastases.5 The higher is Dukes stage that colorectal carcinoma belongs to, the more probability VM appears .6 The tumor cells of colorectal carcinama demonstrated VM highly express MMP-2 , which contribute to the form of VM.