血管内皮生长因子（VEGF）和p53状态在胃癌血管生成中的作用。
The role of vascular endothelial growth factor (VEGF) and p53 status for angiogenesis in gastric cancer.
作者信息
Joo Young Eun, Sohn Young Hae, Joo So Young, Lee Wan Sik, Min Sang Woon, Park Chang Hwan, Rew Jong Sun, Choi Sung Kyu, Park Chang Soo, Kim Young Jin, Kim Sei Jong
机构信息
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
出版信息
Korean J Intern Med. 2002 Dec;17(4):211-9. doi: 10.3904/kjim.2002.17.4.211.
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.
背景
血管生成对于肿瘤生长及转移的发展至关重要。血管内皮生长因子（VEGF）具有强大的血管生成活性，并且p53基因的突变被认为可上调VEGF。我们研究的目的是评估这些肿瘤生物标志物对于血管生成的预后意义，相对于从胃癌既定临床病理参数得出的信息。
方法
在本研究中，我们对145例接受根治性手术治疗的胃癌患者的组织样本进行了VEGF和p53表达的免疫组织化学研究。为评估血管生成，使用抗CD34单克隆抗体通过免疫组织化学染色内皮细胞来计数微血管密度（MVD）。
结果
高MVD与肿瘤浸润深度和远处转移显著相关（分别为p = 0.004，0.021）。此外，高MVD患者的总生存率显著低于低MVD患者（p = 0.048）。VEGF的阳性表达与淋巴结和远处转移显著相关（分别为p = 0.040，0.048）。然而，未发现p53表达与各种临床病理参数之间存在显著相关性。VEGF阳性肿瘤的MVD高于VEGF阴性肿瘤（p = 0.028）。p53的表达与VEGF表达不相关。而且，p53表达状态与MVD之间的关系无统计学显著差异。在多变量分析中，VEGF状态、p53表达和MVD不是独立的预后因素。
结论
VEGF似乎是血管生成的一个重要的、临床相关诱导因子，并且通过MVD评估的血管生成可能是预测胃癌转移的一个有用标志物。然而，需要进一步研究以阐明p53对血管生成的影响以及血管生成在胃癌中的预后意义。
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