Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

Abstract : 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 (CK8/18), and lobular markers (ECAD).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.