Basic research on antlangiogenic drug to prevent metastasls of gastric cancer

为探讨缺氧诱导因子(HIF)-1α和p53表达对人胃癌预后的影响，分析肿瘤的临床病理特征及临床转归。采用免疫组化方法研究了216例原发性胃癌标本中HIF-1α和p53蛋白的表达。HIF-1α (+)/p53（+）肿瘤较HIE-1α (-) /p53（-）肿瘤多为未分化型、浸润性生长、浸润性淋巴累及。HIF-1α (+)/p53（+）肿瘤的淋巴结转移率高于HIF-1α (+)/p53（+）肿瘤。在HIF-1α和p53阳性分层时，p53阴性和HIF-1α阴性患者预后最好，p53阳性和HIF-1α阳性患者预后最差（P=0.0018）。多因素Cox回归分析显示，浸润深度、淋巴结转移、HIF-1α阳性是影响胃癌患者预后的独立因素。HIF-1α是胃癌的独立预后因素之一，HIF-1α蛋白过表达与无功能p53的结合预示着胃癌预后较差。

To investigate the impact of expression of hypoxia-inducible factor (HIF)-1α and p53 on prognosis in human gastric cancer, the clinicopathological characteristics of tumor and clinical outcome were analyzed. Expression of HIF-1α and p53 proteins were studied by immunohistochemistry in 216 specimens of primary gastric cancer. HIF-1α (+)/p53(+) tumors were more frequently undifferentiated type, infiltrative growth appearance, invasive in lymphatic involvement than could be the HIE-1α (-)1p53(-) ones. HIF-1α (+)/p53(+) tumors also had more lymph node metastasis than did HIF-1α (+)/p53(+) ones. When stratified for HIF-1α and p53 positivity, the patients with p53-negative and HIF-1α -negative had the most favorable prognosis and those with p53-positive and HIF-1α -positive had the worst one (P=0.0018). Using multivariate Cox regression analysis, depth of invasion, lymph node metastasis, and HIF-1α positivity were independent prognostic factors in the patients with gastric cancer. HIF-1α is one of the independent prognostic factors in gastric cancer, and the combination of HIF-1α protein overexpression with nonfunctional p53 indicates a dismal prognosis.