ABSTRACT
Vascular endothelial growth factor (VEGF) is known to play a key role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on esophageal carcinoma and the correlation between VEGF and p53. Tissue samples were taken from 81 patients with esophageal carcinoma after surgery. VEGF and p53 expressions were examined by immunohistochemical staining. Microvessels in the tumor stained for CD34 antigen were also counted. VEGF and p53 expressions were observed in 51.3% (41/80) and 51.9% (41/79), respectively. The microvessel density was 70.9+/-6.7 (mean+/-SE) in VEGF-positive group and 68.7+/-5.1 in VEGF-negative group. However, no correlation was noted between VEGF and p53 expression. Whereas the tumor size, nodal status, depth of invasions, and tumor stage were associated with poor overall survival, VEGF expression or p53 expression was not. These results indicate that VEGF and p53 are highly expressed in esophageal carcinomas. Since the VEGF expression is not correlated with the p53 expression, microvessel density or clinicopathological findings, further studies with other angiogenic molecules are needed to determine the role in esophageal carcinomas.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Capillaries , Carcinoma, Squamous Cell/classification , Endothelial Growth Factors/biosynthesis , Esophageal Neoplasms/classification , Lymphatic Metastasis , Lymphokines/biosynthesis , Neoplasm Staging , Neovascularization, Pathologic , Prognosis , Retrospective Studies , Tumor Suppressor Protein p53/biosynthesis , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
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 immunohistochemical 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.