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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-1α、VEGF过表达及高MVD与结直肠癌的不良生物学行为有关。
Objective To investigate the relationship between the expression of tumor suppressor gene p53 and hypoxia inducible factor-1α (HIF-1α) and the angiogenesis and biological behavior of colorectal cancer. Methods The expressions of p53, HIF-1α, VEGF and MVD in 61 colorectal cancer tissues were detected by immunohistochemistry. Results The positive rates of HIF-1α in colorectal cancer tissues were 65.6%. The positive rate of HIF-1α expression in colorectal cancer tissues was 27.9%, 19.7% and 18.0% respectively. The positive rates of p53 and VEGF were 42.6% and 49.2% , MVD averaged 28.7 ± 12.9. HIF-1α, VEGF expression and MVD are closely related to the depth of tumor invasion, lymph node metastasis, liver metastasis and Dukes stage. The expression of p53 is closely related to lymph node metastasis and liver metastasis. The positive rates of p53, VEGF and MVD were positively correlated with the positive expression of HIF-1α (correlation coefficients were 0.261, P <0.05; 0.591, P <0.01; 0.795, P <0.01). Conclusion The HIF-1α / VEGF pathway plays an important role in the angiogenesis of colorectal cancer tissues. The inactivation of p53 gene may promote tumor angiogenesis via HIF-1α / VEGF pathway. p53 gene inactivation, HIF-1α, VEGF overexpression and high MVD are associated with adverse biological behavior of colorectal cancer.