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目的:探讨胃腺癌中缺氧诱导因子-1α(HIF-1α)mRNA、血管内皮生长因子(VEGF)和MVD的表达,探讨其间的相互关系及临床意义。 方法:应用原位杂交和免疫组化方法检测HIF-lαmRNA、VEGF蛋白的表达,用CD-34单克隆抗体标记肿瘤微血管密度。 结果:胃腺癌组HIF-1αmRNA、VEGF的阳性表达率分别为76.7％和66.7％,明显高于正常对照组的20％和0％,胃腺癌组的MVD为34±10,高于正常对照组的15±5,(P<0.01),MVD表达与肿瘤的分化隋况,即病理分型密切相关,(P<0.01);而与TNM分期、淋巴结转移和远处转移情况无明显相关性。VFGF阳性表达率与TNM分期表现出一定的相关性,而与病理分型无关,发生远处转移者的VEGF阳性表达率81.9％,高于无远处转移者52.6％(P<0.05)。HIF-1αmRNA表达与MVD呈正相关(r=0.37,P<0.05);与VEGF表达也表现出正相关性(r=0.42,P<0.05);而VFGF表达与MVD并无相关(r=0.19,P>0.05)。 结论:胃腺癌HIF-1αHIF-1αmRNA过度表达与肿瘤中血管生成密切相关,HIF-1α可以通过诱导VEGF生成而刺激肿瘤血管生成,但这一路径并不是HIF-1α影响肿瘤的血管生成的唯一路径。
Objective: To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) mRNA, vascular endothelial growth factor (VEGF) and MVD in gastric adenocarcinoma, and to explore the relationship between them and clinical significance. Methods: The expression of HIF-1αmRNA and VEGF protein were detected by in situ hybridization and immunohistochemistry. The density of tumor microvessels was marked by CD-34 monoclonal antibody. Results: The positive expression rates of HIF-1α mRNA and VEGF in gastric adenocarcinoma group were 76.7% and 66.7%, respectively, which were significantly higher than 20% and 0% in normal control group. The MVD of gastric adenocarcinoma group was 34±10, higher than that in normal control group. At 15±5, (P<0.01), the expression of MVD was closely related to the differentiation status of the tumor, that is, the pathological type, (P<0.01), but there was no significant correlation with the TNM staging, lymph node metastasis, and distant metastasis. The positive expression rate of VFGF showed a certain correlation with TNM staging. Regardless of pathological type, the positive rate of VEGF expression in patients with distant metastasis was 81.9%, which was higher than that of 52.6% without distant metastasis (P<0.05). HIF-1α mRNA expression was positively correlated with MVD (r=0.37, P<0.05); it also showed positive correlation with VEGF expression (r=0.42, P<0.05); but there was no correlation between VFGF expression and MVD (r=0.19, P>0.05). Conclusion: Overexpression of HIF-1αHIF-1α mRNA in gastric adenocarcinoma is closely related to angiogenesis in tumor. HIF-1α can stimulate angiogenesis by inducing VEGF production, but this pathway is not the only pathway that HIF-1α affects tumor angiogenesis. .