HPV-16E6/E7、HIF-1α表达与宫颈癌变及微血管生成相关性研究

目的:探讨不同宫颈病变中HPV-16E6/E7、缺氧诱导因子-1α(HIF-1α)的表达及MVD的变化,分析三者与宫颈癌变及其发展的内在联系。方法:采用免疫组化EnVision法检测45例宫颈鳞癌组织(SCC)、60例宫颈上皮内瘤变组织(CINⅠ～Ⅱ30例,CINⅢ30例)及10例正常宫颈组织(NCE)中HPV-16E6/E7、HIF-1α的表达,并以CD34标记血管内皮细胞计数MVD。结果:随着宫颈病变的进展,HPV-16E6/E7与HIF-1α的阳性表达率逐渐增高,MVD逐渐增大。MVD在以上4组间相比差异均有统计学意义(P<0.05)。HPV-16E6/E7与HIF-1α在宫颈鳞癌、CINⅢ、CINⅠ～Ⅱ、正常宫颈组织中的阳性表达率分别为86.67%、66.67%、46.67%、10.00%与84.44%、63.33%、33.33%、20.00%,且两者在正常组与CINⅠ～Ⅱ组表达率差异均无统计学意义(P>0.05),在其余组间差异有统计学意义(P<0.05)。宫颈鳞癌组织中HIF-1α与HPV-16E6/E7、MVD表达呈正相关性(P<0.05),HPV-16E6/E7与MVD也呈正相关性(P<0.05)。结论:HPV-16E6/E7与HIF-1α在宫颈鳞癌的发生、发展中起着协同作用,HPV-16E6/E7增加、HIF-1α蛋白的表达和稳定性促进宫颈癌血管生成,可能在子宫颈癌变中发挥关键作用。

Research on correlation between HPV-16E6/E7 expression, HIF-1α expression and cervical carcinogenesis, angiogenesis

Objective:To explore the expressions of HPV-16E6/E7,hypoxia inducible factor-1α(HIF-1α) and microvessel density(MVD) in different cervical lesions,analyze their relationship with cervical carcinogenesis and their interrelation.Methods:Immunohistochemical En Vision method was used to detect the expressions of HPV-16E6/E7 and HIF-1α in 45 cases with cervical squamous cell carcinoma,60 cases with cervical intraepithelial neoplasia(CIN)(30 cases with CINⅠ-Ⅱ and 30 cases with CINⅢ),and 10 cases with normal cervix,CD34 was used to label vascular endothelial cells,MVD was counted.Results:With the progress of cervical lesions,the positive expression rates of HPV-16E6/E7,HIF-1α and MVD increased gradually.There was statistically significant difference in MVD among the above-mentioned four groups(P<0.05).The positive expression rates of HPV-16E6/E7 and HIF-1α in cervical squamous cell carcinoma group,CINⅠ-Ⅱ group,CINⅢ group,normal cervix group were 86.67%,66.67%,46.67%,10.00% and 84.44%,63.33%,33.33%,20.00%,respectively,and there was no statistically significant difference in positive expression rates of HPV-16E6/E7 and HIF-1α between CINⅠ-Ⅱ group and normal cervix group,but there were statistically significant differences among the other groups.There was a positive correlation between expressions of HPV-16E6/E7 and HIF-1α and MVD in cervical squamous carcinoma group(P<0.05),there was a positive correlation between HPV16-E6/E7 expression and MVD(P<0.05).Conclusion:HPV-16E6/E7 and HIF-1α play synergic effects in development of cervical squamous cell carcinoma,HPV-16E6/E7 up-regulation and HIF-1α protein expression and stability can promote angiogenesis of cervical carcinoma,which may play key roles in cervical carcinogenesis.