目的： 探讨宫颈鳞状细胞癌（squamous cell carcinoma, SCC）组织中细胞S期激酶相关蛋白2(S-phase kinase associated protein 2,Skp2)检测的临床意义。 方法： 选取来自2004年至2008年上海交通大学第二附属医院和延边妇幼医院病理科的25例正常宫颈鳞状上皮组织、84例宫颈上皮内瘤变（cervical intraepithelial neoplasia, CIN）组织和163例宫颈SCC组织的存档蜡块，应用PCR法检测病变组织中HPV的感染情况，以免疫组化法检测Skp2蛋白在上述组织中的表达并分析其临床预后评估价值。 结果： Skp2蛋白在所有25例正常宫颈鳞状上皮组织中表达阴性，在宫颈SCC组织中表达率为84.0%（137/163），在CIN-1、CIN-2、CIN-3组织中表达率分别为37.9%（10/29）、81.6%（31/38）、82.4%（14/17），显示Skp2表达率从而高到低为SCC＞CIN＞正常组织，CIN中为CIN-3＞CIN-2＞CIN-1。Skp2蛋白过表达与宫颈SCC患者人乳头状瘤病毒（human papillomvirus,HPV）感染及FIGO分期均密切相关；此外，Skp2阳性表达的无瘤生存率和总生存率分别为55.5%和59.1%，Skp2阴性表达的无瘤生存率和总生存率分别为96.2%和88.5%(Log-rank分别为11530和10.154，均P=0.001)；但Skp2阳性表达与患者的年龄、Ki-67蛋白表达及病理分级等无关。 结论: Skp2蛋白过表达可能是预示宫颈SCC患者不良预后的潜在检测指标。

Objective : To investigate the clinical significance of S-phase kinase-associated protein 2 (Skp2) measurement in the diagnosis and prognosis of cervical squamous cell carcinoma (SCC). Methods: Paraffin-embedded blocks of cervical tissue specimens collected from 25 healthy women, 84 women with cervical intraepithelial neoplasia (CIN) and 163 women with SCC who were cared in the Second People’s Hospital Affiliated to Shanghai Jiaotong University and Yanbian Women’s and Children’s Hospital between 2004 and 2008 were obtained. Protein content of Skp2 and the presence of human papillomavirus (HPV) in these specimens were analyzed by immunohistochemical staining and PCR, respectively. The correlation between Skp2 content and prognostic scores was also analyzed. Results: While Skp2 protein was undetectable in the 25 healthy control subjects, it was detected in 84.0% (137/163) of SCC patients, 37.9% (10/29) of CIN-1 patients, 81.6% (31/38) of CIN-2 patients and 82.4% (14/17) of CIN-3 patients (P<0.01). Skp2 protein content was closely related with HPV infection and the International Federation of Gynecology and Obstetrics (FIGO) clinical stage. The lesion-free survival and overall survival rates were 55.5% and 59.1%, respectively, in Skp2-positive patients and were 96.2% and 88.5% (Log-rank 11.530 and 10.154, P＝001), respectively, in Skp2-negative patients. Skp2 content in the cervical epithelium was not correlated with patient age, Ki-67 expression and pathological grade of cervical cancer. Conclusion: Skp2 may be a biomarker of cervical squamous cell carcinoma cell proliferation and therefore Skp2 protein content measurement may have a clinical significance in the diagnosis and prognosis of cervical cancer.

国家自然科学基金资助项目（No.61371067）；吉林省科技厅中青年创新团队领军人才项目资助（No.20130521017JH）