Ki-67 quantitative evaluation as a marker of cervical intraepithelial neoplasia and human papillomavirus infection.
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-67-positive 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-67-positive nuclei per 100-mum basal membrane, which were more frequent in the middle and upper third layers of the epithelium compared with low-risk HPV and HPV-negative cases (P < 0.001). The differences among the CIN groups in the total number and in the percentages of Ki-67-positive 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-67-positive 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.
Mimica
Marko
M
Gynenova Policlinic, Istarska 21, 21000 Split, Croatia. marko.mimica1@st.t-com.hr
Tomić
Snjezana
S
Kardum
Goran
G
Hofman
Irena Drmić
ID
Kaliterna
Vanja
V
Pejković
Lidija
L
D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis* / Q000378:metabolism; D008297:Male; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D004279:DNA, Viral; D019394:Ki-67 Antigen