The role of vascular endothelial growth factor (VEGF) and p53 status for angiogenesis in gastric cancer.
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.


CONCLUSIONS
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.
Joo
Young Eun
YE
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Sohn
Young Hae
YH
Joo
So Young
SY
Lee
Wan Sik
WS
Min
Sang Woon
SW
Park
Chang Hwan
CH
Rew
Jong Sun
JS
Choi
Sung Kyu
SK
Park
Chang Soo
CS
Kim
Young Jin
YJ
Kim
Sei Jong
SJ
D000328:Adult; D000368:Aged; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D016228:Endothelial Growth Factors; D016159:Tumor Suppressor Protein p53