ArticleOncotarget2017
Quantification of HER2 and estrogen receptor heterogeneity in breast cancer by single-molecule RNA fluorescence in situ hybridization.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Molecular shifts in breast cancer following neoadjuvant chemotherapy: a prospective study and review of literature.Future oncology (London, England) · 2025Review
- Mapping cancer biology in space: applications and perspectives on spatial omics for oncology.Molecular cancer · 2024Review
- Article
- Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections.Genome biology · 2023Article
- Quantification of spatial pharmacogene expression heterogeneity in breast tumors.Cancer reports (Hoboken, N.J.) · 2023Article
- Article
- Article
- Loss of HER2 in breast cancer: biological mechanisms and technical pitfalls.Cancer drug resistance (Alhambra, Calif.) · 2022Article
- Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions.Nature communications · 2021Article
- The Known Unknowns of the Immune Response toJournal of fungi (Basel, Switzerland) · 2021Review
- Heterogeneity in Signaling Pathway Activity within Primary and between Primary and Metastatic Breast Cancer.Cancers · 2021Article
- Review
- Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise.Cancers · 2020Review
- Spatially multiplexed RNA in situ hybridization to reveal tumor heterogeneity.Nucleic acids research · 2020Article
- Cholesterol signaling in single cells: lessons from STAR and sm-FISH.Journal of molecular endocrinology · 2018Review
- RollFISH achieves robust quantification of single-molecule RNA biomarkers in paraffin-embedded tumor tissue samples.Communications biology · 2018Article
- Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer.Nature communications · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intra-tumor heterogeneity is a pervasive property of human cancers that poses a major clinical challenge. Here, we describe the characterization, at the transcriptional level, of the intra-tumor topography of two prominent breast cancer biomarkers and drug targets, epidermal growth factor receptor 2 (HER2) and estrogen receptor 1 (ER) in 49 archival breast cancer samples. We developed a protocol for single-molecule RNA FISH in formalin-fixed, paraffin-embedded tissue sections (FFPE-smFISH), which enabled us to simultaneously detect and perform absolute quantification of HER2 and ER mature transcripts in single cells and multiple tumor regions. We benchmarked our method with standard diagnostic techniques, demonstrating that FFPE-smFISH is able to correctly classify breast cancers into well-established molecular subgroups. By counting transcripts in thousands of single cells, we identified different expression modes and levels of inter-cellular variability. In samples expressing both HER2 and ER, many cells co-expressed both genes, although expression levels were typically uncorrelated. Finally, we applied diversity metrics from the field of ecology to assess the intra-tumor topography of HER2 and ER gene expression, revealing that the spatial distribution of these key biomarkers can vary substantially even among breast cancers of the same subtype. Our results demonstrate that FFPE-smFISH is a reliable diagnostic assay and a powerful method for quantification of intra-tumor transcriptional heterogeneity of selected biomarkers in clinical samples.
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