The Use of Tumor Heterogeneity Scoring in Determining the Amount of Tissue Required for HER2 Diagnosis in Breast Cancer
Steven J Potts, Holger Lange, David G Young, Nicholas Landis, David A Eberhard. Flagship Biosciences, Flagstaff, AZ; University of North Carolina, Chapel Hill, NC
Background: Effective clinical approaches to measuring tumor heterogeneity would be useful in both evaluating patient therapeutic response as well as determining the amount of tissue required for diagnosis. Combining methodology based on current clinical anatomic practice with ecological diversity statistics, we created a new scoring system that combines tumor and cell level heterogeneity called the HetMap, that allows visualization of the heterogeneity of a subject in the context of an entire patient population.
Design: We evaluated the approach on HER2 immunohistochemistry stained breast cancer samples, using 200 specimens across two different laboratories, with three pathologists at each laboratory outlining ten to twenty regions of tumor for scoring. by automatic cell-baed image analysis. HetMap was evaluated using three different scoring schemes: HER2 scoring according to ASCO/CAP guidelines, H-Score and a new continous HER2 score (HER2cont). We determined the extent to which heterogeneity and the area of tissue analyzed contributes to disconcordance rates between pathologists.
Results: Two definitions of heterogeneity, cell-level and tumor-level, provided useful independent measures of heterogeneity. Cases with higher disconcordance rates showed a statistically significant correlation with higher tumor heterogeneity. As the area analyzed increased, the disconcordance rates decreased.
Conclusions: HetMap is a general approach that can be applied to any marker and was here evaluated using the IHC HER2 maker for breast cancer tissue. The results suggest that HetMap could be a useful means to identify tumors with higher degrees of heterogeneity, or to highlight slides that should be rechecked for QC issues.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 46, Wednesday Morning