The Pilot Study Of Vasculogenic Mimicry In Lung Cancer And The Relation Between Apoptosis And Vasculogenic Mimicry

Objective:Study the expression of vasculogenic mimicy in lung cancer. Analyze its correlation with lung cancer metastasis, different clinicopathologic parameter, and the survival and prognostic of patients. Further analyze the role of apoptosis in VM formation, and demonstrate the clinical significance of VM and the anti-apoptotic preliminary as a new therapeutic target.Method:Collecting lung cancer 500 samples from 2002 to 2008 at our Hospital. Observe VM under high power lens. Analyze VM positive rate by double-staining technique. Study the difference of VM expression in different clinicopathologic parameter by chi square test. Analyze the prognostic of VM by single and multy factor survival analysis. Study several apoptosis indexes'expression in VM positive group and negative group. Detect apoptosis index differences in VM positive and negative groups by Tunnel Method.Result:1. Observe HE slices under optical microscope to find cases which contains VM.90 cases with rich blood supply and with the VM and mosaic vessels characteristics were selected out from 500 patients, clinical and follow-up information is completely.65 patients were males, and 25 female; Age of 25 to 78-year-old, with a median age of 56.5; 49 cases of SCC,7 cases of adenocarcinoma, 23 cases of SCLC,4 cases of carcinoid, and 7 cases of large cell carcinoma; I a period of 17 cases, I b 14 cases,Ⅱa 4 cases,Ⅱb 22 cases,Ⅲa 13 cases,Ⅲb 18 cases, IV stage 2 patients.34 cases had lymph node metastasis.2. CD31, PAS double-staining to determine the expression of VMThe double-staining result is 32 cases of VM, and the positive rate is 35.6%.But from the perspective of 500 cases, the positive rate was 6.4%. In VM-positive group, distant metastasis rate is 81.25%, and in negative group is 55.2%.The two groups had statistically significant (x2=4.678, P= 0.031).VM positive rate in T1 period of 52.2%, T2 period of 41.9%, T3+T4 period of 19.4%, three have statistically significant difference (x2=7.401, P=0.025). Otheres have no statistically significant difference. 3. Survival analysis results of 90 cases All 90 cases were divided into two groups by VM, namely, VM-positive group and the VM-negative group. Kaplan-Meier univariate survival analysis the survival rate of the two groups, parallel Log-rank test,and the difference was statistically significant (VM-positive group and the VM-negative group, median survival time were 18 months and 25 months, Log-Rank=5.955, P=0.015); Cox multivariate survival analysis showed that lymph node metastasis (OR=0.512, P=0.023) and postoperative distant metastases (OR=0.139, P=0.000) can be used as two independent risk factors for lung cancer patients.4. The expression of apoptosis index in the VM-positive group and negative groupIn the VM-positive group and negative group, P53 protein positive rates were 53.1% and 54.8%, no significant difference between the two groups; Bcl-2 protein were 25% and 54.8%, difference between the two groups was statistically significant (χ2=5.857,P=0.016);Cyt-c protein were 46.9% and 38.7%,but no significant difference between the two groups; Caspase-8 protein were 31.3% and 9.7%, difference was statistically significant (χ2= 4.474, P= 0.034); Caspase-9 protein were 21.9% and 9.7%, no significant difference between the two groups; Caspase-3 protein were 59.4% and 32.3%, difference was statistically significant(χ2= 4.661, P= 0.031).Apoptotic index in VM-positive group is (4.06±1.638)%, and in VM negative group is(2.47±1.663)%.The difference was statistically significant (p=0.008).Conclusion:1. There is vasculogenic mimicry in lung cancer, and the VM has relation to distant metastasis and tumor T-staging.2. Apoptosis-related proteins and apoptotic index was higher in VM-positive group. So we can see apoptosis for the formation of VM has certain significance.3. For the VM patients, targeted therapy should be taking into account the vascular endothelial cells and tumor cells in two ways. In addition, if the apoptosis as an initiators of the formation of VM in lung cancer, then the antagonist apoptosis antibody is expected to become targeted therapy as EGFR-TKI.