Expression Of VEGF-C, VEGF-D And MMP-2 In Human Gastric Carcinoma And Their Relationship To Lymph Node Metastasis

Gastric carcinoma is one of the common digestive carcinomas. Studies showed that it was one of the leading causes of cancer death. Metastasis is the leading cause of death. In principle, cancer cells can spread within the body by different mechanisms, including local tissue invasion, direct seeding of body cavities or surfaces, hematogenous spread and lymphatic spread. Among these, lymphatic spread is a very common pattern for most cancer cells. Early gastric carcinoma can spread through lymphatic pattern, and this deeply affects patient's survival.Vascular endothelial growth factor-C(VEGF-C) and Vascular endothelial growth factor-D(VEGF-D) are the specific lymphatic endothelial growth factors. They can bind their specific receptor VEGFR-3 (Vascular endothelial growth factor recepor-3) to induce lymphangiogenesis. In addition to their important role in regulating lymphangiogesis, they can enhance lymphatic metastasis. Their expression in human gastric carcinoma has positive correlation with lymph node metastasis.The important obstacle for cancer cells' metasteses is matrixes. Matrix Metalloproteinase 2(MMP-2) can degrade the type VI collagen and destroy the matrixes, enhance cancer cells' invasive and metastatic abilities. MMP-2 plays an important role in the infiltration and metasteses of cancer cells.In order to investigate the possible mechanism of the lymphatic metastasis ofgastric carcinoma and the clinicopathological significance of VEGF-C,VEGF-D and MMP-2 expression in gastric carcinoma, an immunohistochemical SABC(Strept Avidin Biotin Complex) method was used to examine the expression of the three kinds of proteins.Materials and Methods (1) 63 surgically resected gastric carcinoma samples and 20 normal gastric mucosa were collected. All the tissues were fixed in 10% neutral formalin and embedded in paraffin. (2) SABC immunostaining technique was used to examine the expression of VEGF-C, VEGF-D and MMP-2 in normal gastric mucosa and gastric carcinoma. (3) The data were analysed by software SPSS 11.0, Chi-Square test or Fisher's exact test and Spearman correlation test were used to compare the differences between different groups. A difference was considered significant if the P value was below 0.05.Results :(1) In normal gastric mucosa, staining for VEGF-C protein was negative. Positive staining in gastric carcinoma was heterogeneous, and its positive rate was 44.4%. There was significant difference in the expression of VEGF-C between normal mucosa group and carcinoma group(/><0.01). There was no expression of VEGF-D in normal gastric mucosa. Positive staining for VEGF-D protein in gastric carcinoma was not even and diffuse, and its positive rate was 41.3%. There was significant difference in the expression of VEGF-D between the two groups(P<0.01). hi normal gastric mucosa , positive staining for MMP-2 protein was even, and the positive rate was 15%. Positive staining for MMP-2 protein in gastric carcinoma was not even and diffuse, and its positive rate was 54.0%. There was significant difference in the expression of MMP-2 between the two groups(P<0.01).(2) According to the degree of differentiation of gastric carcinoma, the cases were divided into high/moderate differentiation group and poor differentiation group. In the two groups, the positive rates of VEGF-C were 29.6% and 55.6% respectively, and there was significant difference between the two groups(/><0.05). The positive rates of VEGF-D were 25.9% and 52.8% respectively, and there was significant difference between the two groupsP0.05) . The positive rates of MMP-2 were 37.0% and 66.7% respectively, and there was significant difference between the twogroups(P<0.05).(3) According to the infiltrating depth of gastric carcinoma, 63 cases were divided into with serosa infiltration group and without serosa infiltration group. The positive rates of VEGF-C were 56.1% and 22.7% respectively. There was significant difference between the two groups0.05 The positive rates of VEGF-D were 53.7% and 18.2% respectively. There was significant di...