宫颈腺癌中HPV感染与Skp2、p27^(kip1)蛋白表达的研究

Study of HPV infection in cervical adenocarcinoma and relation to expressions of Skp2 and p27^(kip1) protein

目的探讨S期激酶相关蛋白2(Skp2)和细胞周期调控因子p27kip1在宫颈腺癌发生发展中的作用,分析高危型人乳头瘤病毒(HPV)感染与Skp2、p27kip1蛋白表达关系。方法采用组织微阵列技术结合原位杂交和免疫组化(二步法)检测HPV16/18DNA和Skp2、p27kip1蛋白在86例宫颈腺癌和24例慢性宫颈炎组织中的表达。结果宫颈腺癌组HPV16/18DNA与Skp2蛋白阳性表达率分别为65.1%和68.6%,均显著高于慢性宫颈炎组(P<0.01)。p27kip1蛋白在宫颈腺癌组中的阳性表达率为55.8%,明显低于慢性宫颈炎组(P<0.05)。HPV16/18感染与宫颈腺癌病理分级和组织学类型无明显相关性,但与Skp2表达呈正相关(P<0.05),与p27kip1表达呈负相关(P<0.05)。Skp2表达与宫颈腺癌的病理分级有关,G2、G3组阳性表达率均明显高于G1组(P<0.05)。Skp2和p27kip1表达与宫颈腺癌组织学类型有明显相关性。结论宫颈腺癌的发生与HPV16/18感染及Skp2、p27kip1蛋白的表达异常相关,三者协同作用导致宫颈腺癌恶性发展。

[Objective] To study the roles of S-phase kinase-associated protein2 （Skp2） and cell cycle regulator p27kip1 in occurrence and development of cervical adenocarcinoma, and to analyze the relationship between the infection of human papilloma virus （HPV） and the expressions of Skp2 and p27kip1 protein. [Methods] The expressions of HPV16/18DNA and Skp2, p27kip1 protein were determined by tissue microarray combined with in situ hybridization and immunohistochemistry in 86 cases of cervical adenocarcinoma and 24 cases of cervical chronic inflammation. [Results] The positive rates of HPV16/18DNA and Skp2 protein in cervical adenocarcinoma were 65.1% and 68.6% respectively, which significantly higher than that in cervical chronic inflanunation（P 〈0.01 ）. The positive rate of p27kip1 protein in cervical adenocarcinoma was 55.8%, which significantly lower than that in cervical chronic inflammation（P 〈0.05）. There was no relationship between HPV16/18 infection and the pathological grades or histological subtypes, otherwise, there was positive correlation between HPV16/18 infection and Skp2 expression （P 〈 0.05）, there is negative correlation between HPV16/18 infection and p27kip1 expression. The expression of Skp2 was related to the pathologieal grades, the positive rate of Skp2 was signifieantly higher in G2 and G3 than in G1 （P 〈 0.05）. The expressions of Skp2 and p27kip1 were related to the histological types. [Conclusion] Carcinogenesis of cervical adenoeareinoma may be related to the infection of HPV16/18 and the abnormal expressions of Skp2 and p27kip1. Their synergistic reaction may lead to the development of cervical adenoearcinoma.