膀胱癌中缺氧诱导因子-1α和血管内皮生长因子与P53基因表达相关性的初探

The first exploration of the correlation of hypoxia inducible factor-1 alpha,vascular endothelial growth factor and P53 gene expression in bladder cancer

目的探讨膀胱癌中缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)与P53基因表达及其与临床的关系。方法采用免疫组织化学SABC法对196例膀胱癌患者的组织标本分别进行VEGF,HIF-1α及P53免疫组化染色,分析这三种标志物与临床分期和细胞分级的关系及VEGF/HIF-1α在瘤细胞中的共表达情况,并就P53与VEGF/HIF-1α表达的相关性进行对比分析。结果膀胱癌患者中VEGF,HIF-1α和P53的阳性表达率分别为70.5%,57.2%和49.3%。同时提示非肌层浸润和分化好的低级别膀胱癌患者中VEGF,HIF-1α和P53表达水平低于肌层浸润和分化差的高级别患者,两者相比,差异具有统计学意义(P<0.05),VEGF/HIF-1α间表达呈正相关(P<0.05),其中共表达率为48.6%(92/196),P53与VEGF和HIF-1α阳性表达也呈正相关(P53vs VEGF P<0.01,P53vs HIF-1αP<0.05)。结论 VEGF/HIF-1α共表达提示在肿瘤组织细胞中存在VEGF/HIF-1α信号转录现象,P53与VEGF/HIF-1α表达的相关性,表明突变型P53基因可能参与了肿瘤组织的新生血管形成。重视三者的相互影响,有助于提高膀胱癌患者的预后判断及复发风险预测,对分子靶向用药的基因治疗也可能具有一定指导意义。

Objective To investigate the expression of hypoxia inducible factor-1 alpha（HIF-1 alpha）,vascular endothelial growth factor（VEGF）and P53 gene in bladder cancer and their relationship with clinical manifestations.Methods The immunohistochemical SABC method was used to detect the relationship between the three markers and the clinical staging and cell classification and the co expression of VEGF/HIF-1 alpha in the tumor cells,and the correlation between the P53 and the expression of VEGF/HIF-1 awas compared with the expression of P53 and VEGF/HIF-1 alpha in 196 cases of bladder cancer.The relationship between the three markers and the clinical staging and cell classification was analyzed.Results The positive rates of VEGF,HIF-1 and P53 in bladder cancer patients were 70.5%,57.2% and 49.3% respectively.At the same time,the expression of VEGF,HIF-1 alpha and P53 in low grade bladder cancer patients with non myometrium infiltration and differentiation was lower than that of myometrium infiltration and differentiation.The difference was statistically significant（P〈0.05）,and the expression of VEGF/HIF-1 a was positively correlated（P〈0.05）,and the co expression rate was 48.6%（92/196 There was also a positive correlation between P53 and VEGF and HIF-1 alpha positive（P53 vs VEGF P0.01,P53 vs HIF-1 alpha P〈0.05）.Conclusion VEGF/HIF-1 alpha co expression suggests the existence of VEGF/HIF-1 alpha signal transcription in tumor tissue cells,and the correlation between P53 and VEGF/HIF-1 alpha expression,indicating that the mutant P53 gene may be involved in the formation of neovascularization of tumor tissue.It is helpful to improve the prognosis of the patients with bladder cancer and to predict the risk of recurrence.It may also be of certain guiding significance to the gene therapy of molecular targeting drugs for the three patients.