Please select Print from the file menu or right mouse click and choose print from the menu to print this page.

[187] A New Rabbit Monoclonal Antibody (RMab), 4B5, for the IHC Determination of HER2 Status in Breast Cancer: Comparison with CB11 and FISH with Interlaboratory Reproducibility (IR)

WC Powell, DG Hicks, N Prescott, J Pettay, RB Nagle, DJ Dabbs, KM Scott, RW Brown, T Grogan, PC Roche, R Tubbs. Ventana Medical Systems, Inc, Tucson, AZ; Roswell Park Cancer Institute, Buffalo, NY; Cleveland Clinic Foundation, Cleveland, OH; University of Arizona Health Sciences Center, Tucson, AZ; UPMC-Magee Womens Hospital, Pittsburgh, PA; University of Texas Health Science Center Medical School, Houston, TX

Background: The two methodologies in clinical use to assess HER2 status in breast cancer are: FISH (gene amp) and IHC (protein over-expression). A consistent finding has been that 3-15% of breast cancers over-express HER2 protein without evidence for gene amplification. Accurate determination of the HER2 status has implications for selecting patients most likely to respond to Trastuzumab. We report here our experience with a new anti-HER2 RMab, 4B5.
Design: The evaluation of HER2 status in two different cohorts of breast cancer cases (Single institution (SI) and multinational (MN)) with a total of 322 breast cancer cases was performed on an automated staining system (Ventana Medical Systems) and scored by 3 pathologists (0-3+), for comparison with CB11 staining results, and FISH. IR of staining and interpretation was determined on a subset of the SI based cohort at 3 laboratories.
Results: RMab 4B5 demonstrated sharper membrane staining with less cytoplasmic and stromal background staining than CB11. In the SI cohort, the staining results for 4B5 were highly comparable to those obtained for CB11 with an overall concordance of 93.3%. In the MN cohort, the concordance with CB11 was 84.7%. However, 4B5 had a much higher overall agreement with FISH (88.2%), compared to agreement of CB11 with FISH (81.2%). The difference in the performance of CB11 in the MN cohort versus the SI cohort may be due to differences in tissue fixation and processing in a centralized, high volume laboratory in an academic medical center versus multiple sites in the international community with potentially non-standardized techniques.
Conclusions: The results with 4B5 indicate that it has a more robust performance than CB11 since the correlation of 4B5 with FISH was nearly equivalent (88.2% MN; 89.3% SI) in both cohorts. IR was also excellent (Kappa 1.0). RMab 4B5 provides excellent sensitivity, specificity, and IR for the detection of HER2 status in breast cancer.
Category: Breast

Wednesday, March 28, 2007

Poster # 12, Wednesday Morning