Interobserver Variability in the Quantification of MIB-1 Labeling Index on Cytologic Samples from Well Differentiated Neuroendocrine Tumors (WDNETs) of the Pancreas (P) and Gastrointestinal Tract (GIT): A Comparative Analysis of Three Methods
Adele D Fung, Cynthia Cohen, Sravankumar Kavuri, Xin Gao, Michelle D Reid. Emory University School of Medicine, Atlanta, GA; Georgia Health Sciences University, Augusta, GA
Background: WDNETs of the P and GIT are classified in part by measuring MIB1 index. We determined the level of interobserver variability among 3 observers in the calculation of MIB1 labeling index by counting positive cells/400 tumor cells and doing eyeball estimation of MIB1 percentage (%) in 22 WDNETs to determine reliability/reproducibility of both tests compared to the automated cellular imaging system (ACIS, Dako).
Design: Twenty-two WDNETs of the P (n=13), GIT (n=4) and 5 liver metastases (2 colonic, 3 from P) were confirmed by cytology and immunohistochemistry. These were stained with MIB1 antibody (1;160 dilution, Dako, Carpinteria, CA). Number of MIB1-positive cells/400 tumor cells was calculated by 2 cytopathlogists (MR, SK) and 1 fellow (AF). In addition, the 3 reviewers did an eyeball estimate of MIB1% and scored cases into 3 categories; < 2%, 3-20% and > 20%. Statistical analysis using Spearman's correlation coefficient for all observers and methods was performed and compared to that obtained by ACIS.
Results: There was strong statistically significant correlation among observers when calculating MIB1-positive cells/400 tumor cells and when doing an eyeball estimate of MIB1%.
|AF vs SK||0.83||(0.63, 1.0)||<0.05|
|AF vs MR||0.95||(0.88, 1.0)||<0.05|
|SK vs MR||0.88||(0.73, 1.0)||<0.05|
|"Eyeball" Estimate of MIB-1 Index|
|AF vs SK||0.75||(0.48, 1.0)||<0.05|
|AF vs MR||0.86||(0.69, 1.0)||<0.05|
|SK vs MR||0.79||(0.55, 1.0)||<0.05|
|MIB1/400 vs Eyeballing||0.78||(0.53, 1.0)||<0.05|
|MIB1/400 vs ACIS||0.53||(0.14, 1.0)||<0.05|
|Eyeballing vs ACIS||0.62||(0.23, 1.0)||<0.05|