Objective: To investigate the association between p16, p53 and Ki-67 expression and high-risk human papilloma virus (HPV) infection in cervical intraepithelial neoplasia (CIN).
Methods: Using a self-prepared tissue microarray, p16, p53, and Ki-67 expression was detected in 243 cases of CIN and 30 cases of normal cervical epitheliums by immunohistochemistry, and high-risk HPV infection was detected by gene hybridization capture II.
Results: p16, p53 and Ki-67 expressions were all negative in normal cervical epitheliums, but all positive in CIN. The expression of p16 and Ki-67 was 88.2 (67/76) and 92.1% (70/76) in CIN grade 1, respectively, and both were 100% in CIN grades 2 and 3, and the intensity of positive expression was significantly correlated with CIN grade (P<0.001). The positive cells in CIN grade 1 were mostly within the lower 1/3 of the squamous epithelium, while in CIN grade 2, the positive cells involved the lower 2/3 of the epithelium layers; in CIN grade 3, more than 2/3 or almost the full thickness of the epithelium was involved, suggesting significant correlation between the involvement and CIN grades (P<0.001). p53 expression was positive in 31.6% (24/76) of the cases in CIN grade 1, 53.4% (47/88) in CIN grade 2 and 58.2% (46/79) in CIN grade 3, and the intensity of positive expression was in significantly correlation with CIN grades (P<0.001), but no significant difference occurred between CIN 2 and CIN 3. High-risk HPV were detected in 37/52 (71.2%) of the cases in CIN grade 1, 50/58 (86.2%) in CIN 2 and 50/55 (90.9%) in CIN 3, and the relative DNA amount was significantly correlated with CIN grade (P<0.001), but there as no significant difference between CIN 2 and CIN 3.
Conclusions: High-risk HPV infection and p16, p53, Ki-67 overexpression all play important roles in the carcinogenesis of cervical precancerous lesion, and both p16 and Ki-67 expression are useful markers in diagnosis and staging of CIN.