cyclin E、pl6ink4、ki67在宫颈脱落细胞中的表达及其与HPV16／18感染的相关性

目的研究cyclin E、p16ink4、ki67在宫颈脱落细胞中的表达水平及其与HPV16/18感染的相关性,探讨其对宫颈癌高危人群筛查的意义.方法采用免疫组织化学方法对78例官颈脱落细胞标本进行cyclin E、p16ink4、ki67检测,同时应用多重引物PCR技术检测HPV16/18.结果cyclin E、p16ink4、ki67在宫颈癌细胞中的表达水平均较鳞状上皮非典型增生(ASCUS)差异有统计学意义(P＜0.005);各级宫颈癌细胞中HPV16的阳性率均较ASCUS差异有统计学意义(x2=25.27,P＜0.005),且随着宫颈上皮细胞损伤程度加重阳性率升高,差异也有统计学意义(P＜0.01).p16ink4和ki67在宫颈癌细胞中的表达水平与HPV16高度相关(rs=1.0,P＜0.05);而cyclin E的表达与HPV16相关性较小(rs=0.4,P＜0.05).HPV18阳性例数较少,在各项分析中差异均无统计学意义(x2=3.68,P＞0.05).结论官颈癌细胞中cyclin E、p16ink4及ki67的高度表达与HPV16感染有关;它们均可能作为有价值的诊断指标应用于宫颈癌高危人群筛查,且cyclin E对宫颈癌的早期诊断意义更大.

Relations between the expression of cyclin E, p16ink4, ki67 and HPVi6/18 infection in cervical exfoliated cells

OBJECTIVE: To confirm the relations between the expression of cyclin E, p16ink4, ki67 and HPV16/18 infection using cervical exfoliated cells, and evaluate the usefulness of cyclin E, p16ink4 and ki67 as biomarkers for screening of cervical carcinomas. METHODS: The expression of cyclin E, p16ink4 oncoproteins and ki67 proliferative activity was evaluated immuohistochemically in 78 cervical exfoliated epithelial specimens. Human papillomavirus type16 and 18 (HPV16/18) infection was assessed by polymerase chain reaction (PCR) using type specific primers. RESULTS: Cyclin E, p16ink4 and ki67 were all overexpressed in cervical preneoplasia and neoplasia cells, compared with little expressed in ASCUS (P less than 0.005). Overexpression of cyclin E was observed in CIN, (P less than 0.01), p16ink4 and ki67 overexpressed in invasive carcinoma(100 percent and 90.9 percent respectively). The degree of p16ink4 and ki67 expression correlated well with the degree of cervical neoplasia (P less than 0.005). HPV16 infection was assessed at all stages of cervical neoplasia samples, and a significant relationship with the degree of cervical epithelial lession was observed at the same time. The expression level of p16ink4 and ki67 seemed to be more closely associated with HPV16 infection than cyclin E did (rs=1.0 vs rs=0.4). HPV18 was found positive in only 1 case in CIN1 and in 4 cases in CIN2-3. Therefore no significance was found on statistical analysis (P less than 0.005). CONCLUSION: Cyclin E, p16ink4 and ki67 should be regarded as useful biomarkers of HPV-related cervical neoplasias, and be used for screening patients at high risk for developing cervical carcinomas. Moreover, cyclin E might be a significant cytologic marker for the primary screening of cervical carcinomas.