Significance of cyclin E, pl6ink4a and ki67 Overexpression in Cervical Exfoliated-cell Specimens for Primary Screening of HPV-related Cervical Carcinoma

The aim of this study is to investigate cyclin E, pl6inkda and ki67 as possible diagnostic biomarkers for cervical preneoplasia using cervical exfoliated-cell specimens, and evaluate the significance for screening patients at high risk of developing cervical carcinoma. The expression of cyclin E, pl6inkda and ki67 was examinated in 78 cervical exfoliated epithelial specimens diagnosed as atypical squamous cells of undetermined significance (ASCUS) (12 cases), cervical intraepithelial neoplasia (CIN) of type 1 (17 cases), CIN2_3 (38 cases) and invasive carcinoma (11 cases) using immunohistochemical analysis, and simultaneously, the DNA status of human papillomavims (HPY) type 16/18 was detected by polymerase chain reaction (PCR) using type specific primers, cyclin E, pl6inkda and ki67 were all overexpressed in CINs and invasive carcinoma, compared with little expression in ASCUS ( P <0.005). Overexpression of cyclin E was observed in CIN1(94.1%, X^2 = 21.16, P < 0.01), and p16inkda and ki67 were overexpressed in invasive carcinoma (100% and 90.9% respectively). The degree of pl6inkda and ki67 expression correlated well with that of epithelial lesions ( P < 0.005). HPV16/18 infection was assessed in C1Ns and invasive carcinoma samples, and revealed a significant relationship with the degree of cervical epithelial lession. The expression level of pl6inkda and ki67 seemed more closely associated with HPVI6 infection than that of cyclin E (rs= 1.0 vs rs=0.4). Only 1 case in CINI and d cases in CIN2-3 of HPV18 positive samples were detected. Therefore no statistical significance was found by statistical analysis. Overexpression of cyclin E, pl6inkda and ki67 in CINs and invasive carcinoma cells demonstrates the potential use of cyclin E, pl6inkda and ki67 as diagnostic biomarkers for HPV-related cervical neoplastic lesions. In addition, this technique can be used for screening patients at high risk of developing cervical carcinoma.