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1.
Cell Rep Med ; 4(3): 100977, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36921599

RESUMO

Although breast cancer mortality is largely caused by metastasis, clinical decisions are based on analysis of the primary tumor and on lymph node involvement but not on the phenotype of disseminated cells. Here, we use multiplex imaging mass cytometry to compare single-cell phenotypes of primary breast tumors and matched lymph node metastases in 205 patients. We observe extensive phenotypic variability between primary and metastatic sites and that disseminated cell phenotypes frequently deviate from the clinical disease subtype. We identify single-cell phenotypes and spatial organizations of disseminated tumor cells that are associated with patient survival and a weaker survival association for high-risk phenotypes in the primary tumor. We show that p53 and GATA3 in lymph node metastases provide prognostic information beyond clinical classifiers and can be measured with standard methods. Molecular characterization of disseminated tumor cells is an untapped source of clinically applicable prognostic information for breast cancer.


Assuntos
Linfonodos , Humanos , Metástase Linfática/patologia , Prognóstico , Linfonodos/diagnóstico por imagem , Linfonodos/patologia
3.
Cell Syst ; 6(1): 25-36.e5, 2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-29289569

RESUMO

To build comprehensive models of cellular states and interactions in normal and diseased tissue, genetic and proteomic information must be extracted with single-cell and spatial resolution. Here, we extended imaging mass cytometry to enable multiplexed detection of mRNA and proteins in tissues. Three mRNA target species were detected by RNAscope-based metal in situ hybridization with simultaneous antibody detection of 16 proteins. Analysis of 70 breast cancer samples showed that HER2 and CK19 mRNA and protein levels are moderately correlated on the single-cell level, but that only HER2, and not CK19, has strong mRNA-to-protein correlation on the cell population level. The chemoattractant CXCL10 was expressed in stromal cell clusters, and the frequency of CXCL10-expressing cells correlated with T cell presence. Our flexible and expandable method will allow an increase in the information content retrieved from patient samples for biomedical purposes, enable detailed studies of tumor biology, and serve as a tool to bridge comprehensive genomic and proteomic tissue analysis.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Citometria por Imagem/métodos , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Quimiocina CXCL10/análise , Quimiocina CXCL10/genética , Feminino , Células HeLa , Humanos , Hibridização In Situ/métodos , Queratina-19/análise , Queratina-19/genética , Proteômica/métodos , RNA Mensageiro/análise , Receptor ErbB-2/análise , Receptor ErbB-2/genética , Análise de Célula Única/métodos
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