@article{10.1172/jci.insight.87030, author = {Anup Sood AND Alexandra M. Miller AND Edi Brogi AND Yunxia Sui AND Joshua Armenia AND Elizabeth McDonough AND Alberto Santamaria-Pang AND Sean Carlin AND Aleksandra Stamper AND Carl Campos AND Zhengyu Pang AND Qing Li AND Elisa Port AND Thomas G. Graeber AND Nikolaus Schultz AND Fiona Ginty AND Steven M. Larson AND Ingo K. Mellinghoff}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Multiplexed immunofluorescence delineates proteomic cancer cell states associated with metabolism}, year = {2016}, month = {5}, volume = {1}, url = {https://insight.jci.org/articles/view/87030}, 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.}, number = {6}, doi = {10.1172/jci.insight.87030}, url = {https://doi.org/10.1172/jci.insight.87030}, }