MIB-1 Index as a Surrogate for Mitosis-Karyorrhexis Index in Neuroblastoma

Abstract

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.

A three-dimensional bioprinted model to evaluate the effect of stiffness on neuroblastoma cell cluster dynamics and behavior

“…In fact, we observed that a similar increase of cells in the proliferative phase and with high mRNA processing index occurs at 4 weeks culture, nearly reaching the expression values found in 2D cell cultures. The high MKI values obtained are consistent with the characteristic SK-N-BE(2) aggressiveness found in malignant NB [29][30][31] , and also demonstrate that this cell line could be adequately replicated in a high stiffness ECM (2020) 10:6370 | https://doi.org/10.1038/s41598-020-62986-w www.nature.com/scientificreports www.nature.com/scientificreports/ proliferative tumor model. The higher increase found in the antiapoptosis marker (Bcl2), cell proliferation and mRNA processing index, compared with those found in the apoptosis marker (Bax) and the individual increases in stiffness, confirm that the cells adapt more efficiently with the highest stiffness.…”

Prediction for Mitosis-Karyorrhexis Index Status of Pediatric Neuroblastoma via Machine Learning Based 18F-FDG PET/CT Radiomics

“…The International Neuroblastoma Pathology Classification (INPC) is based on age at diagnosis, differentiation grade of the neuroblasts, MKI, and the presence or absence of Schwannian stromal development [ 3 , 4 ]. Using the INPC system, neuroblastoma INPC classification is a strong prognostic index: favorable histology neuroblastoma has an overall survival of 84%, while 45% for unfavorable histology neuroblastoma [ 5 ]. The MKI refers to the total number of cells undergoing karyorrhexis or in mitosis, based on the assessment of a minimum of 5000 tumor cells.…”

“…For tumors that are highly mitotic, or at the opposite end of the range, MKI can be reliably estimated as high or low, respectively. For tumors that are closer to the cutoff values between intermediate and high or low and intermediate, or inconsistent from field to field, a more careful evaluation of MKI is essential [ 5 ]. Despite the progress in computer-assisted technology and image analysis, accurate evaluation of MKI status still faced some challenges.…”

A Novel Online Nomogram Established with Five Features before Surgical Resection for Predicating Prognosis of Neuroblastoma Children: A Population-Based Study

“…Additionally, molecular biology research has found new markers that may replace MKI, such as MIB-1. 35 There is also controversy over the cut-off points for diploidy, triploidy, and hyperdiploidy. 36 The present study showed significant associations between a ploidy value of strictly 1.0 and poor prognosis.…”