Neuroblastoma, the most common extracranial solid tumor in infancy, shows marked biological heterogeneity. Multiple prognostic markers are combined to risk-stratify neuroblastoma patients for treatment. One marker assesses histology, dividing patients into favorable and unfavorable categories based, in part, on the mitosis-karyorrhexis index (MKI). The recommended scoring of 5000 cells is, however, time-consuming and observer-dependent, and accurate counts may not always be performed. In the present study, we investigated using MIB-1 as a surrogate marker for the MKI. Twenty-five cases of neuroblastoma, ranging from low to high MKI, were immunostained for MIB-1. A total of 375 microscopic fields were digitally captured with >100,000 cells scored. The MIB-1 index was determined by image analysis and MKI, by manual counting of the same immunostained fields. There was a significant correlation between the MIB-1 index and MKI comparing all fields (r=0.7869, P<0.01) and an even better correlation comparing individual cases (r=0.9147, P<0.01). Using a linear regression model, a formula was generated to calculate MKI from the MIB-1 index as follows: MKI=(MIB-1 index×0.124)+1.412. With this formula, a low MKI corresponds to an MIB-1 index <4.74, intermediate MKI to an MIB-1 index of 4.74 to 20.87, and high MKI to an MIB-1 index >20.87. For comparison, the calculations were repeated using a manual MIB-1 count on the same images. Similar significant correlations were obtained, with nearly identical cutoff values for MKI categories. This approach can facilitate determination of the MKI by assessing the MIB-1 index, either by image analysis or manual counting.
本研究中我们探讨用MIB-1指数替代MKI的可行性。25例神经母细胞瘤，MKI范围从低、中到高，均行MIB-1染色。数码拍摄了375个视野，评分的细胞数大于100,000个。通过图像分析获得MIB-1指数，MKI则由人工计数相同视野得出结果。将所有的视野对比， MIB-1 指数和MKI显著相关(r=0.7869, P<0.01)；单个视野对比，两者的相关性更强(r=0.9147, P<0.01)。用线性回归模型分析，得出用MIB-1指数计算MKI的公式： MKI=(MIB-1指数×0.124)+1.412。运用该公式，低MKI对应的MIB-1指数 <4.74，中mki对应的mib-1指数范围4.74—20.87，高mki对应的mib-1指数>20.87。作为对照，用人工计数方法重复计算同一图像的MIB-1指数。MIB-1指数和MKI同样存在显著相关性，MKI对应的MIB-1指数分界值几乎相同。