Aim: To investigate integrin beta3 mRNA and vascular endothelial growth factor (VEGF) protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis.
Methods: In situ hybridization(ISH) of integrin beta3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer.
Results: The positive rate of integrin beta3 mRNA in non-tumor gastric mucosa (20%) was significantly lower than that of the gastric cancer tissue (52.5%, c2 = 10.20, P < 0.01). In patients of infiltrating type, stage T(3)-T(4), vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin beta3 mRNA were significantly higher than those in patients of expanding type (P < 0.01), stage T(1)-T(2) (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. In patients of infiltrating type, stage T(3)-T(4), vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type (P < 0.01), stage T(1)-T(2) (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. In patients of infiltrating type, stage T(3)-T(4), vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type (P < 0.01), stage T(1)-T(2) (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. It was found that the positive expression rate of integrin beta3 mRNA was positively related to that of VEGF protein (P < 0.01) and MVD (P < 0.05), meanwhile the positive expression rate of VEGF protein was positively related to MVD (P < 0.05). The mean survival period in patients with positive expression of integrin beta3 mRNA and VEGF, and MVD > or = 54.9/mm(2) was significantly shorter than that in patients with negative expression of integrin beta3 mRNA (P < 0.05) and VEGF (P < 0.01), and MVD < 54.9/mm(2) (P < 0.01). Five-year survival rate in patients with positive expression of integrin beta3 mRNA and VEGF, and MVD > or = 54.9/mm(2) was significantly lower than those with negative expression of integrin beta3 mRNA (P < 0.05), VEGF (P < 0.05), and MVD < 54.9/mm(2) (P < 0.01).
Conclusion: Integrin beta3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.