Ki-67 expression in squamous intraepithelial lesions of the uterine cervix

BACKGROUND: Uncontrolled cell proliferation and malignant transformation are the basic elements in the development of malignant disease including cervical cancer and its precursors. The aim of this study was to investigate the proliferative activity by using Ki-67 proliferative marker according to CIN grade. METHODS: We used immunohistochemical methods to study the expression of the proliferative marker Ki-67 in the specimens of 5 patients with normal cervical epithelium, 7 with CIN1, 13 with CIN2, and 25 patients with CIN3 grade of the cervical intraepithelial lesions. RESULTS: All cases with normal cervical epithelium and all those with CIN1 changes had negative proliferative Ki-67 index. Ki-67 positive proliferative index was found in 5 (38.46%) and 17 (68%) of patients with CIN2 and CIN3 changes respectively. There was a clear trend for increasing number of cases with positive Ki-67 index with increasing CIN grade. High significant difference of Ki-67 expression was found between patients with CIN1 and CIN2 lesions (t=2.9; p<0.01). Ki-67 positive cells were distributed only in the lower third of the epithelial layer in CIN1 cases. Seven (53.8%) and 13 (52%) of patients with CIN2 and CIN3 changes respectively, had Ki-67 positive cells in the lower and middle third of the epithelial layer, while 3 (23.1%) and 10 (40%) of cases with the same dysplastic changes had Ki-67 positive cells distributed in lower, middle and upper third of the epithelium. Difference of the Ki-67 positive cells distribution was highly significant between patient with CIN1 and CIN2 epithelial changes. CONCLUSION: The present study shows that there is statistically significant relation between proliferative activity, distribution of Ki-67 positive cells, and CIN grade. Ki-67 antigen could be a tool to identify women who are at higher risk for progression and/or recurrence of cervical squamous precancerous lesions.