Expression of survivin in gastric cancer and its relationship with tumor angiogenesis

Abstract

Survivin, a member of inhibitors of apoptosis, has been found in various human cancers. Its expression is associated with tumor progression and adverse outcome. Angiogenesis is an essential process for the primary tumor to grow and invade the adjacent normal structures. Angiogenic factors such as vascular endothelial growth factor induce survivin expression in endothelial cells. The current study was designed to investigate the possible role of survivin and vascular endothelial growth factor status for angiogenesis in human gastric cancer. In this study, we conducted an immunohistochemical investigation of survivin and vascular endothelial growth factor expression in 106 tissue samples obtained from gastric cancer patients undergoing surgical treatment. To assess tumor angiogenesis, microvessel density was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody. The positive expression of survivin and vascular endothelial growth factor in gastric cancer tissues was demonstrated in 50.0 and 69.8% of cases, respectively. The expression of survivin did not associate with vascular endothelial growth factor expression. Expression of survivin was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival (P=0.011, 0.004, 0.020, 0.002, 0.046, respectively). High microvessel density was significantly associated with lymph node metastasis and poor survival (P=0.006 and 0.017, respectively). The mean microvessel density value of survivin positive tumors was 87.4+/-34.4 and significantly higher than that of survivin negative tumors (P=0.016). The mean microvessel density value of vascular endothelial growth factor positive tumors was 98.7+/-37.0 and significantly higher than that of vascular endothelial growth factor negative tumors (P=0.001). A combined analysis of survivin and vascular endothelial growth factor status showed that the mean microvessel density value of both positive tumors was 103.7+/-33.1 and significantly higher than that of both negative tumors (P<0.001). These results suggest that survivin may play an important role in carcinogenesis by stimulating tumor angiogenesis in human gastric cancer.