title: Interobserver variability associated with the MIB-1 labeling index: high levels suggest limited prognostic usefulness for patients with primary brain tumors.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Allegheny General Hospital and MCP Hahnemann University, Pittsburgh, Pennsylvania 15212, USA. dgrzybic@wpahs.org
authors.forename: D M
authors.initials: DM
authors.lastname: Grzybicki
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: S A
authors.initials: SA
authors.lastname: Moore
authors.forename: H G
authors.initials: HG
authors.lastname: Brown
authors.forename: J F
authors.initials: JF
authors.lastname: Silverman
authors.forename: F
authors.initials: F
authors.lastname: D'Amico
authors.forename: S S
authors.initials: SS
authors.lastname: Raab
mesh_terms: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000473:pathology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D019394:Ki-67 Antigen; D009687:Nuclear Proteins / Q000032:analysis*; D015588:Observer Variation; D011379:Prognosis; D012680:Sensitivity and Specificity
chemical_list: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009687:Nuclear Proteins