Image Cytometric Proliferation (MIB-1): Interinstitutional and Interobserver Validation
Clinton E McElroy, Douglas M Minot, Diane H Lawson, Jesse S Voss, Amy C Clayton, Aziza Nassar, Cynthia Cohen. Emory University School of Medicine, Atlanta, GA; Mayo Clinic College of Medicine, Rochester, MN
Background: Proliferation (MIB-1 labeling index [LI]) is used to assess prognosis, and hence, management in breast carcinoma, gastrointestinal tract, neuroendocrine, and brain tumors. Thus, LI needs to be accurately quantitated. Two institutions with a total of three observers performed a validation study in order to assess concordance of results between institutions and among observers.
Design: Two sets of 30 formalin fixed paraffin-embedded breast carcinomas, chosen at institution 1 were immunostained (IHC)(Dako MIB-1 antibody) at two institutions designated 1 and 2 respectively. Quantification was by image cytometry (IA)(ACIS, Dako) by three observers (A,B,C). Results from IHC1/IA1 were compared to those from IHC2/IA2 by observers A and C respectively, who routinely perform daily quantitation. The results of IHC1/IA1, IHC2/IA2, IHC1/IA2, IHC2/IA1 each quantitated by A, B, and C were compared using cutoffs low (≤ 10%), intermediate (11-20%), and high (>20%).
Results: Substantial agreement was demonstrated between both institutions and observers despite differences in both analytical and preanalytical variables.
|IHC1/IA1 vs. IHC2/IA1||26/30 (87%)||0.89|
|IHC1 A/B||25/30 (83%)||0.79|
|IHC1 A/C||27/30 (90%)||0.74|
|IHC1 B/C||24/30 (80%)||0.86|
|IHC2 A/B||22/30 (73%)||0.63|
|IHC2 A/C||22/30 (73%)||0.65|
|IHC2 B/C||24/30 (80%)||0.68|
|Institution 1||Ventana platform, Hematoxylin||8-10 average representative fields, 40X|
|Institution 2||Dako autostainer,Light Hematoxylin||3 “Hotspots”, 20X|