Ki-67 quantitative evaluation as a marker of cervical intraepithelial neoplasia and human papillomavirus infection

Abstract

Objective: To assess the value of Ki-67 quantitative analysis in cervical intraepithelial neoplasia (CIN) in relation to CIN grading and human papillomavirus (HPV) group typing. Methods: Cervical samples selected retrospectively from 106 cases were analyzed immunohistochemically for Ki-67Ypositive nuclei in 3 epithelial layers and by polymerase chain reaction for HPV typing. Results: The proportion of high-risk HPV positivity was 0% in normal controls and 30% in CIN 1, 57% in CIN 2, and 90% in CIN 3 groups, and there was no low-risk HPV finding in CIN 2 and CIN 3 cases (P < 0.001). High-risk HPV-positive cases exhibited significantly more Ki-67Ypositive nuclei per 100-Km basal membrane, which were more frequent in the middle and upper third layers of the epithelium compared with low-risk HPV and HPVnegative cases (P < 0.001). The differences among the CIN groups in the total number and in the percentages of Ki-67Ypositive nuclei in the lower, middle, and upper third layers of the epithelium were significant (P < 0.001). With the cutoff value of more than 33% Ki-67Ypositive nuclei in the middle and the upper third layers of the epithelium, Ki-67 staining demonstrated 98.4% sensitivity (60/61 cases) and 97.8% specificity (44/45 cases) for the detection of CIN 2/CIN 3 in our study group. Conclusions: The Ki-67 immunostaining proved to be predictive for high-risk HPV infection, and it can differentiate reactive lesions from cervical dysplasias. Ki-67 quantitative analysis in 3 epithelial layers is a sensitive and specific method of differentiation between CIN 1 and CIN 2/CIN 3 grades and can be a valuable adjunctive method for more accurate CIN grading. Copyright © 2010 by IGCS and ESGO.