Abstract: Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IHC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

Abstract: Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IHC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

Abstract: A method for predicting responsiveness to a HER2-directed therapy by assessing HER2 heterogeneity in a tumor includes contacting a sample of the tumor with a biomarker-specific reagent that specifically binds to HER2 protein and detecting HER2 protein in the sample, contacting the sample of the tumor with a first nucleic acid probe that specifically binds HER2 genomic DNA and detecting HER2 gene amplification status in the sample, contacting the sample of the tumor with a second nucleic acid probe that specifically binds HER2 RNA and detecting HER2 RNA status in the sample scoring the HER2 protein (IHC), HER2 gene (DISH), and HER2 RNA (RNA-ISH), predicting that the tumor is responsive to the HER2-directed therapy if the tumor reveals a first foci having a first score and a second score, in which the first score and the second score are not the same.

Abstract: Disclosed herein are methods for detecting the presence and/or amount of HER2 protein, HER2 nucleic acid (for example, HER2 genomic DNA), ER protein, and Chromosome 17 centromere DNA in a single sample. Samples stained for HER2 protein, HER2 DNA, ER protein, and Chromosome 17 DNA allow for the identification of various types of cancer cells, for example HER2 protein positive/ER protein positive/HER2 gene positive cells, HER2 protein positive/ER protein negative/HER2 gene positive cells, HER2 protein negative/ER protein positive/HER2 gene positive cells, and HER2 protein negative/ER protein negative/HER2 gene positive cells.

Abstract: Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IHC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

Abstract: Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IHC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

Abstract: Multiplex assays for improved scoring of tumor tissues stained with PD-L1 featuring PD-L1 staining in a first color plus staining of one or more differentiating markers, such as a marker specific for tumor cells and a marker specific for immune cells, are disclosed. The differentiation between the tumor cells and immune cells may improve the ease of scoring, the accuracy and speed of scoring, and the reproducibility of scoring of PD-L1 positive samples for therapy purposes.

Abstract: Disclosed herein are multiplex methods for co-detecting a B cell marker, TP53 nucleic acid, and Chromosome 17 centromere DNA in a single sample. Samples stained for the B cell marker (e.g., CD79a protein), TP53 nucleic acid, and Chromosome 17 centromere DNA may allow for the identification of the subtype of chronic lymphocytic leukemia (CLL) with the 17p deletion. The methods feature staining the B cell marker (e.g., CD79a) a first distinct color, TP53 in a second distinct color, and chromosome 17 centromere DNA in a third distinct color. Further disclosed are nucleic acid probes specific for 19q12, INSR, ATM, DLEU2, TP53, and 13q12.

Abstract: Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IHC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

Abstract: Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IBC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

Abstract: Disclosed herein are methods for predicting the response to a HER2-directed therapy and for scoring a breast cancer tumor sample. In some embodiments, the methods include contacting the sample with an antibody that specifically binds HER2 protein and detecting presence and/or amount of HER2 protein and contacting the sample with a nucleic acid probe that specifically binds to HER2 genomic DNA and detecting presence and/or amount of HER2 genomic DNA (such as HER2 gene copy number). In some embodiments, the methods further include detection of a centromere nucleic acid (such as chromosome 17 centromere DNA) and contacting the sample with an antibody that specifically binds ER protein and detecting presence and/or amount of ER protein in the same sample.

Abstract: The present disclosure relates to systems and methods for analyzing chromosomal translocations, and in particular to analysis of chromosomal translocation by in situ hybridization.

Abstract: Disclosed herein are methods for detecting the presence and/or amount of HER2 protein, HER2 nucleic acid (for example, HER2 genomic DNA), ER protein, and Chromosome 17 centromere DNA in a single sample. Samples stained for HER2 protein, HER2 DNA, ER protein, and Chromosome 17 DNA allow for the identification of various types of cancer cells, for example HER2 protein positive/ER protein positive/HER2 gene positive cells, HER2 protein positive/ER protein negative/HER2 gene positive cells, HER2 protein negative/ER protein positive/HER2 gene positive cells, and HER2 protein negative/ER protein negative/HER2 gene positive cells.

Abstract: The present invention provides compositions and methods for simultaneously detecting mutational status and gene copy number. In particular, the present invention provides simultaneous measurement of gene copy number and detection of the L858R and Exon 19 del mutations in a tissue sample.

Abstract: Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IBC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

Abstract: Multiplex assays for improved scoring of tumor tissues stained with PD-L1 featuring PD-L1 staining in a first color plus staining of one or more differentiating markers, such as a marker specific for tumor cells and a marker specific for immune cells, are disclosed. The differentiation between the tumor cells and immune cells may improve the ease of scoring, the accuracy and speed of scoring, and the reproducibility of scoring of PD-L1 positive samples for therapy purposes.

Abstract: Embodiments of substrates and processes for chromogenic detection, and in particular pyrazolyl dihydrogen phosphate compounds, are disclosed.

Abstract: The present invention provides a method and kit for detection of two or more target molecules in a single tissue sample, such as for gene and protein dual detection in a single tissue sample. Methods comprise treating a tissue sample with a first binding moiety that specifically binds a first target molecule. Methods further comprise treating the tissue sample with a solution containing a soluble electron-rich aromatic compound prior to or concomitantly with contacting the tissue sample with a hapten-labeled binding moiety and detecting a second target molecule. In one example, the first target molecule is a protein and the second is a nucleic acid sequence, the first target molecule being detected by immunohistochemistry and the second by in situ hybridization. The disclosed method reduces background due to non-specific binding of the hapten-labeled specific binding moiety to an insoluble electron rich compound deposited near the first target molecule.

Abstract: Embodiments of substrates and processes for chromogenic detection, and in particular pyrazolyl dihydrogen phosphate compounds, are disclosed.

Abstract: The present invention relates to systems and processes for chromogenic in situ hybridization (CISH), and in particular to methods that prevent interference between two or more color detection systems in a single assay. The present invention also relates to processes for scoring assays utilizing break-apart probes.