摘要目的 探讨skp2在宫颈鳞状细胞癌和癌前病变中的表达规律及其与人乳头状瘤病毒(HPV)感染之间的关系.方法 采用免疫组织化学(ABC法)和原位杂交检测Skp2蛋白和HPV16/18 DNA在30例正常宫颈鳞状上皮、29例宫颈低级别上皮内瘤变、31例高级别上皮内瘤变和31例宫颈鳞状细胞癌中的表达.结果 Skp2在正常宫颈鳞状上皮中呈阴性,与宫颈低级别上皮内瘤变(阳性表达率为13.8%,4/29)之间差异无统计学意义(P>0.05).随着上皮病变级别升高,表达也逐渐增强,在宫颈鳞状细胞癌中表达更强;HPV16/18 DNA在四组中的阳性表达率,除高级别上皮内瘤变和宫颈鳞状细胞癌两组间差异无统计学意义外(均为96.8%),其余各组之间差异均有统计学意义(P<0.01);在宫颈低级别上皮内瘤变中skp2蛋白表达和HPV感染相关无统计学意义,但在高级别上皮内瘤变和宫颈鳞状细胞癌两组中均呈正相关(γ高级别=0.373,γ癌 =0.416,P<0.05).结论 Skp2过表达主要在宫颈鳞状细胞癌形成的中晚期起作用,可作为一个早期诊断恶性的指标,且可能与HPV16/18感染有协同作用.E7-skp2-Rb可能是HPV感染诱导宫颈鳞状细胞癌形成的一条新致癌途径.

abstractsObjective To study the expression of Skp2 in cervical squamons cell carcinoma (SCC) and its precancerous lesions, and to investigate its relationship with human papillomavirus ( HPV ) infection. Methods The expression of Skp2 protein and HPVI6/18 DNA was determined using immunohistochemistry and in-situ hybridization in 30 cases of normal cervical squamous epithelium, 29 cases of low-grade intraepithelial neoplasia, 31 cases of high-grade intraepithelial neoplasia and 31 cases of cervical SCC. Results Skp2 expression was not detected in normal cervical squamons epithelium and no significant difference was obtained statistically on Skp2 expression between normal cervical squamons epithelium and low-grade intraepithelial neoplasia (P>0.05 ). However, the expression of Skp2 gradually increased with elevation of epithelial lesion grading in an order from low to high grade and to cervical SCC (P<0.01). The positive rate of HPV01/18 DNA in cases of normal cervical squamons epithelium, low-grade, high-grade intraepithelial neoplasia and cervical SCC was significantly different (P<0.01), although both high-grade intraepithelial neoplasia and cervical SCC had a similar high HPV infection rate up to 96.8%. There was no correlation obtained between Skp2 expression and HPV16/18 infection in low-grade intrsepithelial neoplaeia. In contrast, expression of Skp2 and HPV infection were significantly correlated in both high-grade intraepithelial neoplasia and cervical SCC ( γH =0.373,γc =0.416,P<0.05). Conclusions Abnormal expression of Skp2 is present mainly in high-grade cervical intranpithelial neoplasia and invasive carcinoma, which may be considered as a surrogate marker for the high-grade lesions. Skp2 may play a key role in the development of cervical squamons carcinoma induced by HPV16/18 infection, through E7-Skp2-Rb signaling pathway.