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JCI Insight. 2016 May 5;1(6). pii: e87030.

Multiplexed immunofluorescence delineates proteomic cancer cell states associated with metabolism.

Author information

  • 1Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA.
  • 2Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • 4Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • 5Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • 6Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • 7Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California, USA.
  • 8Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • 9Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; Department of Pharmacology, Weill Cornell Medical School, New York, New York, USA.

Abstract

The phenotypic diversity of cancer results from genetic and nongenetic factors. Most studies of cancer heterogeneity have focused on DNA alterations, as technologies for proteomic measurements in clinical specimen are currently less advanced. Here, we used a multiplexed immunofluorescence staining platform to measure the expression of 27 proteins at the single-cell level in formalin-fixed and paraffin-embedded samples from treatment-naive stage II/III human breast cancer. Unsupervised clustering of protein expression data from 638,577 tumor cells in 26 breast cancers identified 8 clusters of protein coexpression. In about one-third of breast cancers, over 95% of all neoplastic cells expressed a single protein coexpression cluster. The remaining tumors harbored tumor cells representing multiple protein coexpression clusters, either in a regional distribution or intermingled throughout the tumor. Tumor uptake of the radiotracer 18F-fluorodeoxyglucose was associated with protein expression clusters characterized by hormone receptor loss, PTEN alteration, and HER2 gene amplification. Our study demonstrates an approach to generate cellular heterogeneity metrics in routinely collected solid tumor specimens and integrate them with in vivo cancer phenotypes.

PMID:
27182557
PMCID:
PMC4863708
DOI:
10.1172/jci.insight.87030
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