Bulten J, van der Laak J A, Gemmink J H, Pahlplatz M M, de Wilde P C, Hanselaar A G
Institute of Pathology, University Hospital Nijmegen, Netherlands.
J Pathol. 1996 Mar;178(3):268-73. doi: 10.1002/(SICI)1096-9896(199603)178:3<268::AID-PATH482>3.0.CO;2-4.
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.
采用免疫过氧化物酶技术，使用单克隆抗体MIB1对正常和发育异常的宫颈上皮组织标本（5例CIN1、7例CIN2、5例CIN3和5例正常）进行评估，该抗体识别细胞增殖相关Ki-67抗原上的福尔马林固定抗性表位。使用图像分析系统测量与增殖活性相关的四个参数：Ki-67标记指数（LI）、每单位长度基底膜的Ki-67阳性细胞核数量，以及Ki-67阳性细胞核距基底膜相对距离的最大值和第90百分位数。所有这四个与增殖相关的参数均与上皮发育异常变化的分级高度相关（0.90 < r < 0.97，p < 0.0001）。相对距离的第90百分位数的相关性最佳，使用该参数可正确分类所有CIN病变。正常上皮、CIN1、CIN2和CIN3病变中Ki-67 LI的平均值和标准差分别为0.07±0.03、0.16±0.03、0.25±0.06和0.39±0.06。这些发现支持了CIN涉及宫颈上皮细胞增殖活性进行性功能障碍的理论。MIB1的图像分析是一种有前景的替代方法，可用于对宫颈上皮发育异常变化进行客观、可重复和可靠的分类。
