P53及缺氧诱导因子-1α表达与结直肠癌血管生成的关系

目的探讨抑癌基因p53及缺氧诱导因子-1α(HIF-1α)的表达与结直肠癌血管生成及生物学行为的关系.方法采用免疫组织化学方法检测61例结直肠癌组织中p53、HIF-1α和血管内皮生长因子(VEGF)表达及微血管密度(MVD).结果结直肠癌组织中,HIF-1α阳性表达率为65.6%,其中弱、中、强阳性表达率分别为27.9%、19.7%、18.0%,p53和VEGF阳性表达率分别为42.6%和49.2%,MVD平均为28.7±12.9.HIF-1α、VEGF表达及MVD与肿瘤浸润深度、淋巴结转移、肝转移和Dukes分期密切相关.p53表达与淋巴结转移和肝转移密切相关.p53、VEGF阳性表达率及MVD均与HIF-1α阳性表达程度成正相关(相关系数分别为0.261,P＜0.05;0.591,P＜0.01;0.795,P＜ 0.01).结论HIF-1α/VEGF通路在结直肠癌组织血管 生成过程中起重要作用,p53基因失活可能经HIF-1α/VEGF通路促进肿瘤血管生成.p53基因失活、HIF-1 α、VEGF过表达及高MVD与结直肠癌的不良生物学行为有关.

Study on relationship between expression of P53,HIF-1α and angiogengesis of colorectal carcinoma

Objective: To investigate the impact of HIF-1α expression and its relation with p53 protein overexpression on the angiogenesis and biological behavior of colorectal carcinoma. Methods: Sixty-one samples of colorectal carcinoma tissues were examined for p53, HIF-1α and VEGF expression by SABC immunohistochemical method and for the CD34 endothelial antigen by SP immunohistochemical method to highlight the new growth microvessels, the microvessel density of tumor was calculated. Results: The positive rate of HIF-1α expression was 65.6%, in which the weak, moderate and strong positive expression rates were 27.9%, 19.7% and 18.0%, respectively. The positive rates of p53 and VEGF expression were 42.6 %, 49.2 %, respectively. The mean of MVD was 28.7±12.9 (range from 6 to 55). The expressions of HIF-1α, VEGF and MVD were significantly correlated with the depth of invasion, lymph node metastasis, liver metastasis and Dukes′ stage. The expression of p53 was significantly correlated with lymph node metastasis and liver metastasis. p53 and VEGF expression and MVD were positively correlated with HIF-1α expression (Their relative coefficient were 0.261, P＜0.05; 0.591, P＜0.01 and 0.795, P＜0.01respectively). Conclusions: HIF-1α/VEGF pathway may play an important role in angiogenesis of colorectal carcinoma. Loss of p53 function may facilitate angiogenesis via HIF-1α/VEGF pathway. Loss of p53 function, overexpression of HIF-1α and VEGF and higher MVD are related with the poor biological behavior of colorectal carcinoma.