MIB1, a promising marker for the classification of cervical intraepithelial neoplasia

Formalin-fixed and paraffin-embedded tissue specimens of normal and dysplastic cervical epithelia (five CIN1, seven CIN2, five CIN3, and five normal) were assessed by an immunoperoxidase technique, using the monoclonal antibody MIB1, regonizing a formalin-fixation-resistant epitope on the cell proliferation-associated Ki-67 antigen. An image analysis system was used to measure four parameters associated with proliferative activity: the Ki-67 labelling index (LI), the number of Ki-67-positive nuclei per unit length of basement membrane, and the maximum value and 90th percentile of the relative distances of Ki-67-positive nuclei from the basement membrane. All these four proliferation-related parameters were highly correlated with the grade of dysplastic change in the epithelium (0.90 < r < 0.97, p < 0.0001). The best correlation was found for the 90th percentile of the relative distance and with this parameter all CIN lesions could be correctly classified. The means and standard deviations of the Ki-67 LIs in normal epithelium, CIN1, CIN2, and CIN3 lesions were 0.07 +/- 0.03, 0.16 +/- 0.03, 0.25 +/- 0.06, and 0.39 +/- 0.06, respectively. These findings support the theory that CIN involves a progressive dysfunction of the proliferative activity of cervical epithelial cells. Image analysis of MIB1 is a promising alternative method for the objective, reproducible, and reliable classification of dysplastic changes in cervical epithelium.