Relationship Between Expression Of VEGF,E-cadherin,MMP-2,MMP-1 In Gastric Carcinoma And Its Clinicopathology As Well As Patient Survival

Objective:To study the expression of VEGF,E-cadherin,MMP-2 and MMP-1 in gastric carcinoma and analyze the features of them and the relationship between them with clinicopathology as well as patient prognosis.Methods:200 cases of gastric carcinoma,56 cases of paracancer and 55 cases of lymph nodes were made into tissue microarray.Meanwhile 30 cases of normal gastric tissue were chosen as control.VEGF,E-cadherin,MMP-2 and MMP-1 were detected by immunohistrochemistry staining.Microvessel density(MVD)and microlymphatic density(MLD)were detected by double immunohistrochemistry staining. Kaplan-Meier survival analysis was performed for 111 cases with survival time.We analyzed the prognostic factors by Cox regression model in these cases.Results(1)The positive rates for VEGF of the gastric carcinoma,paracancer and control were respectively 81.5%(163/200),35.7%(20/56)and 10%(3/30).The positive rate for VEGF of the gastric carcinoma was higher than that of the paracancer as well as control(P＜0.001).The positive rates for VEGF of the differentiated gastric carcinoma and undifferentiated gastric carcinoma were 72.6%(69/95)and 89.5%(94/105)respectively.There was significant difference between the two groups(P=0.002).The positive rate for VEGF of diffused gastric carcinoma was higher than that of intestinal gastric carcinoma(P=0.009).(2)The positive rates for E-cadherin of the gastric carcinoma,paracancer and control were respectively 22.0%(44/200),55.4%(31/56)and 100%(30/30).The positive rate for E-cadherin of the gastric carcinoma were lower than that of the paracancer as well as the control(P＜0.001)The positives rates for E-cadherin of the differentiated gastric carcinoma and undifferentiated gastric carcinoma were 33.7% (32/95)and 11.4%(12/105)respectively.There was significant difference between the two groups(P=0.002).The positive rates for E-cadherin of the gastric carcinoma with invasion under serosa and that with invasion out of serosa were respectively 36.5%(19/52)and 16.9%(25/148),the former was higher than the latter(P =0.001).The result of Spearman correlation analysis was that the expression of E-cadherin had negative correlation with the depth of invasion(r=-0.183,P=0.010). The positive rate for E-cadherin of intestinal gastric carcinoma was higher than that of diffused gastric carcinoma(P=0.001).(3)The positive rates for MMP-2 of the gastric carcinoma,paracancer and control were 76%(152/200),26.8%(15/56)and 13.3%(4/30)respectively.The positive rate for MMP-2 of the gastric carcinoma was higher than that of the paracancer as well as the control(P＜0.001).The positive rates for MMP-2 of the gastric carcinoma with invasion under serosa and that with invasion out of serosa were 48.1%(19/52)and 85.8%(127/148)respectively.There was significant difference between the two groups.The positive rates for MMP-2 of the gastric carcinoma with lymph node metastasis and that of those without lymph node metastasis were 89.3% (109/122)and 55.1%(43/78)respectively,the former was higher than the latter (P＜0.001).The positive rates for MMP-2 of the gastric carcinoma whose diameter is bigger than 5cm(φ≥5cm)and that of gastric carcinoma whose diameter is smaller than 5cm(φ＜5cm)were 88.0%(103/117)and 59.0%(49/83)respectively.There was significant difference between the two groups(P＜0.001).(4)The positive rates for MMP-1 of the gastric carcinoma,paracancer and control were 80.5%(161/200),69.6%(39/56)and 20%(6/30)respectively.The positive rate for VEGF of the gastric carcinoma was higher than that of the control(P＜0.001).The positives rates for VEGF of the differentiated gastric carcinoma and undifferentiated gastric carcinoma were 71.6%(68/95)and 88.6%(93/105) respectively.There was significant difference between the two groups(P=0.002).The positive rate for MMP-1 of diffused gastric carcinoma was higher than that of intestinal gastric carcinoma(P=0.001)(5)The MVD of gastric carcinoma,paracancer and control was 28.84±14.17, 17.02±8.54 and 16.69±7.21 respectively.The MVD of gastric carcinoma was higher than that of control(P＜0.001).The MVD of the differentiated gastric carcinoma and undifferentiated gastric carcinoma was 25.53±11.14 and 31.84±15.91 respectively, there was significant difference between the two groups(P=0.001).The MVD of the gastric carcinoma with invasion under serosa and that with invasion out of serosa was 21.81±9.10 and 31.31±14.81 respectively,there was significant difference between the two groups(P＜0.001).The MVD of diffused gastric carcinoma(31.20±15.24) was higher than that of intestinal gastric carcinoma(25.88±12.35)(P=0.009).MVD of gastric carcinoma with positive expression of VEGF and that of gastric carcinoma with negative expression were respectively 31.20±15.24 and 25.88±12.35,there was significant difference between the two groups(P=0.007).The result of Spearman correlation analysis was that the expression of VEGF has a positive correlation with MVD(r=-0.183,P=0.010).(6)The MLD of gastric carcinoma,paracancer and control were respectively 8.55±4.98,4.05±2.48 and 3.99±1.56.The MLD of gastric carcinoma was higher than that of control(P＜0.001).The MLD of differentiated gastric carcinoma and undifferentiated gastric carcinoma was 7.71±4.54 and 9.38±5.16 respectively.There was significant difference between the two groups(P=0.016).The MLD of diffused gastric carcinoma(9.52±5.00)was higher than that of intestinal gastric carcinoma(7.59±4.32)(P=0.005).MLD of gastric carcinoma with lymph node metastasis and that of those without lymph node metastasis was 10.02±5.00 and 6.18±3.35 respectively,there was significant difference between the two groups(P＜0.001).(7)111 cases with survival time were performed by Log-rank test of Kaplan-Meier survival analysis.The survival time of patients with negative VEGF,negative MMP-2 and positive E-cadherin was higher than those of patients with positive VEGF, positive MMP-2 and negative E-cadherin(P＜0.001),respectively.The survival time of patients without lymph node metastasis was higher than that with lymph node metastasis(P＜0.001).The survival time of patients with invasion under serosa was higher than that out of serosa(P＜0.001).The survival time of patients with differentiated gastric carcinoma was higher than that with undifferentiated gastric carcinoma.The survival time of patients with intestinal gastric carcinoma was higher that of patients with diffused gastric carcinoma(P=0.039).(8)VEGF,E-cadherin,MMP-2,depth of invasion and lymph node metastasis were independent prognostic factors by COX regression analysis. Conclusions:1.The expression of VEGF,MMP-2 and MMP-1 was increased in gastric carcinoma, meanwhile E-cadherin was reduced.These indicated that VEGF,MMP-2,MMP-1 and E-cadherin contributed to the process of the genesis and progress of gastric carcinoma.2.The reduced E-cadherin as well as the increased VEGF and MMP-1 maybe was the early incidents of gastric cancer.3.VEGF was closely associated with angiopoiesis of gastric cancer.E-cadherin was closely associated with invasion.MMP-2 was closely associated with invasion,lymph node metastasis and tumor size.VEGF,E-cadherin and MMP-1 were associated with differentiation and Lauren type.4.There was largely proliferation of microvessel and microlymphatic in gastric cancer. MLD was closely associated with lymph node metastasis.5.Such factors as VEGF,MMP-2,E-cadherin,tumor size,differentiation,lymph node metastasis and depth of invasion were closely associated with survival time of patient with gastric cancer.VEGF,MMP-2,E-cadherin,lymph node metastasis and depth of invasion were independent prognostic factors.