[2098] 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.

Comparative Statistics

	Concordance	R2
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

Differences in Preanalytic and Analytic Methods

	Preanalytic	Analytic
Institution 1	Ventana platform, Hematoxylin	8-10 average representative fields, 40X
Institution 2	Dako autostainer,Light Hematoxylin	3 “Hotspots”, 20X

Conclusions: Comparing IHC between institutions using IA from the same institution showed strong agreement with one observer. When IHC from one institution was quantitated at a different institution by 3 different observers, results showed very good or substantial agreement. Standardization of preanalytic and analytic methods as suggested by an international panel of investigators in March, 2010, should improve concordance.
Category: Quality Assurance

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 302, Monday Morning