Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance
Technical Report,01 Jul 2014,30 Jun 2015
University of California, Davis Davis United States
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Current breast cancer diagnosis includes predictive assays to guide therapy decisions, involving a minimum of 3assays ER, PR,and HER2. Many labs also include a marker of proliferation Ki67, and sometimes myoepithelial SMA, epithelial CK818, and lobular markersECAD. Recently, a host of new multi-marker panels developed. The Mammostrat assay Clarient uses a panel of five IHC markers P53,SLC7A5,NRDG1, HTF9C, CEACAM5. Gene-expression assays using qRT-PCR, array hybridization, and RNA sequence assays have also been developed. The OncotypeDX, for example, uses a panel of 21 genes 16 analytical, 5 controls Ki67, STK15, Survivin, CCNB1, MYBL2, MMP11,CTSL2, HER2, GRB7, GSTM1,CD68, BAG1, ER, PGR, BCL2, SCUBE2, ACTB, GAPDH, RPLPO, GUS, TFRC to stratify risk of recurrence, and relative benefit of adjuvant chemotherapy. This explosion in biomarkers poses both cost and logical selection challenges. In addition, these assays generally lose all spatial context information including heterogeneity. MIBI technology provides the potential to simultaneously assay all of the relevant analytes in an intact tissue architecture, with submicron resolution and a greatly expanded dynamic range of quantitation. We propose to develop assays and analysis tools to evaluate breast cancer tissues using formal fixed and paraffin embedded tumor tissues from the clinic, and we will compare the utility of the MIBI platform assays to the current assays. Our objective is to validate MIBI as an alternative to current standard multi-gene assays. We also hypothesize that MIBI breast cancer data will improve the ability to stratify risk and predict therapy responses by taking into account the distribution and heterogeneity of molecularly defined cell populations in breast cancer.