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Updated: Jul 21, 2026
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Interobserver variability associated with the MIB-1 labeling index: high levels suggest limited prognostic usefulness
D M Grzybicki1, Y Liu, S A Moore
1Department of Pathology and Laboratory Medicine, Allegheny General Hospital and MCP Hahnemann University, Pittsburgh, Pennsylvania 15212, USA. dgrzybic@wpahs.org
Background:
The use of the MIB-1 labeling index (LI) as a potential prognostic marker for patients with primary brain tumors is controversial. Many studies advocating its prognostic usefulness have suggested discrete MIB-1 LI cut-off values, above which patients have significantly worse outcomes. However, interobserver variability associated previously with MIB-1 LI calculation has not been reported despite the fact that the degree of interobserver variability impacts the clinical usefulness of such cut-off values.
Methods:
MIB-1 LIs were calculated independently using a standardized protocol by six pathologist observers for 50 astrocytic gliomas of varying grades. The level of interobserver agreement was determined by calculating kappa statistics for pairwise pathologist comparisons using MIB-1 LI cut-off values of 2.5%, 5.0%, 8.0%, 11.0%, and 15.0%. Spearman rank correlation coefficients were used to assess the pairwise associations between observer MIB-1 LIs.
Results:
Although there was general agreement among pathologists regarding whether an MIB-1 LI for a given astroglial tumor was low, moderate, or high based on the analysis of correlation, a high level of interobserver variability was associated with the determination of specific MIB-1 LIs. The highest level of agreement occurred using a cut-off value of 5.0%, with pairwise kappa statistics for this value ranging from 0.52 to 0.80.
Conclusions:
The high level of interobserver variability suggests that proposed discrete MIB-1 LI prognostic cut-off values most likely are not useful clinically for predicting outcome for individual patients with primary brain tumors. Further prospective studies are needed investigating the prognostic usefulness of MIB-1 LI ranges that optimize interobserver agreement.
