The Role of Vascular Endothelial Growth Factor VEGFand p53 Status for Angiogenesis in Gastric Cancer

Abstract

Background :Angiogenesis is of crucial importance for tumor growth and development of metastases. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and mutations of the p53 gene has been thought to upregulate VEGF. The purpose of our study was to evaluate the prognostic significance of these tumor biomarkers for angiogenesis relative to the information derived from established clinicopathological parameters in gastric cancer.Methods :In this study, we conducted an immunohistochemicai investigation of VEGF and p53 expression in 145 tissue samples obtained from gastric cancer patients undergoing curative surgical treatment. To evaluate angiogenesis, microvessel density (MVD) was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody.Results :High MVD was significantly associated with depth of tumor invasion and distant metastasis (p=0.004, 0.021, respectively). Moreover, overall survival for patients with high MVD were significantly lower than that of low MVD (p=0.048). Positive expression of VEGF correlated significantly with lymph node and distant metastasis (p=0.040, 0.048, respectively). However, no significant correlation was found between p53 expression and various clinicopathological parameters. VEGF positive tumors showed a higher MVD than VEGF negative tumors (p=0.028). The expression of p53 did not correlate with VEGF expression. Also, the relationship between the status of p53 expression and MVD had not statistically significant differences. In the multivariate analysis, status of VEGF, p53 expression and MVD were not an independent prognostic factor.Conclusion :VEGF seems to be an important, clinically relevant inducer of angiogenesis and angiogenesis assessed by the MVD may be a useful marker for predicting metastasis in gastric cancer. However, further studies are warranted to clarify the impact of p53 on the angiogenesis and the prognostic significance of angiogenesis in gastric cancer.

Expression of Activated Signal Transducer and Activator of Transcription 3 Predicts Expression of Vascular Endothelial Growth Factor in and Angiogenic Phenotype of Human Gastric Cancer

“…Studies on the association between MVD and prognosis in gastric cancer have produced inconsistent results; some have found that MVD is a predictor of poor prognosis, whereas others have found that MVD predicts good prognosis (11, 13, 15, 29 -35). In the present study, overall survival was significantly lower in patients with a high MVD than in patients with a low MVD, which is consistent with several previous reports (11,14,32,33,36,37). However, multivariate analysis revealed that MVD was not an independent prognostic indicator, whereas Stat3 was.…”

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

“…In fact, our results suggest that p53 and VEGF regulate tumour angiogenesis in patients with gastric cancer, but they do not support the fact that p53 stimulates the appearance of new vasculature by enhancing the expression of VEGF. Reviewing the literature, we found three clinical studies with similar findings as ours, confirming that the expression of p53 does not correlate with VEGF expression in gastric cancer patients Giatromanolaki et al, 2000;Joo et al, 2002).…”

Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer

“…VEGF production has been found to be regulated by growth factors, cytokines, oncogenes, anti-oncogenes and other extra cellular molecules, such as hypoxia, p53 gene, TGF-α [28][29][30][31][32] . But few investigations have been concerned with relationship between VEGF and iNOS.…”