P5-11-17: Evaluating Tumor Heterogeneity in Immunohistochemistry Stained Breast Cancer Tissue.

Abstract

Abstract Context: Quantitative clinical measurement of heterogeneity in immunohistochemistry staining would be useful in both evaluating patient therapeutic response and identifying underlying issues in histopathology laboratory quality control. Objective: To create a heterogeneity scoring approach (HetMap) that allows the visualization of an individual patient's IHC heterogeneity in the context of a population. Design: We combined HER2 semi-quantitative analysis with the use of ecology diversity statistics to evaluate cell-level heterogeneity (consistency of protein expression within neighboring cells in a tumor nest) and tumor-level heterogeneity (differences of protein expression across a tumor as represented by a tissue section). We evaluated the approach on HER2 immunohistochemistry stained breast cancer samples, using 200 specimens across two different CLIA laboratories, with three pathologists at each laboratory each outlining regions of tumor for scoring by automatic cell-based image analysis. HetMap was evaluated using three different scoring schemes: HER2 scoring according to ASCO/CAP guidelines, H-Score and a new continuous HER2 score (HER2cont). Results: Two definitions of heterogeneity, cell-level and tumor-level, provided useful independent measures of heterogeneity. Cell-level heterogeneity, reported either as an average or the maximum area of heterogeneity across a slide, had low levels of dependency on the pathologist choice of region (coefficient of variation of 15%). Tumor-level heterogeneity measurements had more dependence on the pathologist choice of regions (coefficient of variation of 25%). Results were highly similar between the two laboratories, which is encouraging for HER2 standardization, as the labs involved different pathologists, different specimens, and different standardization procedures, although both complied with CLIA/CAP guidelines for HER2 testing. Conclusions: HetMap is a measure of heterogeneity, by which pathologists, oncologists, and drug development organizations can view cell-level and tumor-level heterogeneity for a patient for a given marker in the context of an entire patient cohort. Heterogeneity analysis can be a useful means to identify tumors with higher degrees of heterogeneity, or to highlight slides that should be rechecked for QC issues. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-17.