ArticlePloS one2014
In situ quantitative measurement of HER2mRNA predicts benefit from trastuzumab-containing chemotherapy in a cohort of metastatic breast cancer patients.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Pooled it
- RNAscope-based HER2 mRNA detection shows high concordance with fluorescenceTranslational cancer research · 2026Article
- Co-clinical trial targeting ER, FGFR and CDK4/6 in resistant hormone-positive breast cancer with FGFR alterations.NPJ precision oncology · 2025Article
- RNA sequencing and immunohistochemistry jointly improve tumor biomarker interpretation.Scientific reports · 2025Article
- A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response.Cell reports. Medicine · 2024Article
- Quality Assessment of Proteins and RNA Following Storage in Archival Formalin-Fixed Paraffin-Embedded Human Breast Cancer Tissue Microarray Sections.Biopreservation and biobanking · 2023Article
- QuantISH: RNA in situ hybridization image analysis framework for quantifying cell type-specific target RNA expression and variability.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- RNAScopeFrontiers in veterinary science · 2021Article
- Spatially multiplexed RNA in situ hybridization to reveal tumor heterogeneity.Nucleic acids research · 2020Article
- Article
- In situ analysis of FGFR2 mRNA and comparison with FGFR2 gene copy number by dual-color in situ hybridization in a large cohort of gastric cancer patients.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2018Article
- Simultaneous Multiplexed Imaging of mRNA and Proteins with Subcellular Resolution in Breast Cancer Tissue Samples by Mass Cytometry.Cell systems · 2018Article
- Article
- Rapid Loss of RNA Detection by In Situ Hybridization in Stored Tissue Blocks and Preservation by Cold Storage of Unstained Slides.American journal of clinical pathology · 2017Article
- Glucagon-Like Peptide-1 Receptor Expression in Normal and Neoplastic Human Pancreatic Tissues.Pancreas · 2016Article
- Araguspongine C induces autophagic death in breast cancer cells through suppression of c-Met and HER2 receptor tyrosine kinase signaling.Marine drugs · 2015Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundWe sought to determine the predictive value of in situ mRNA measurement compared to traditional methods on a cohort of trastuzumab-treated metastatic breast cancer patients.
methodsA tissue microarray composed of 149, classified as HER2-positive, metastatic breast cancers treated with various trastuzumab-containing chemotherapy regimens was constructed. HER2 intracellular domain(ICD), HER2 extracellular domain(ECD) and HER2 mRNA were assessed using AQUA. For HER2 protein evaluation, CB11 was used to measure ICD and SP3 to measure ECD of the HER2 receptor. In addition, HER2 mRNA status was assessed using RNAscope assay ERRB2 probe. Kaplan - Meier estimates were used for depicting time-to-event endpoints. Multivariate Cox regression models with backward elimination were used to assess the performance of markers as predictors of TTP and OS, after adjusting for important covariates.
resultsHER2 mRNA was correlated with ICD HER2, as measured by CB11 HER2, with ECD HER2 as measured by SP3 (Pearson's Correlation Coefficient, r = 0.66 and 0.51 respectively) and with FISH HER2 (Spearman's Correlation Coefficient, r = 0.75). All markers, HER2 mRNA, ICD HER2 and ECD HER2, along with FISH HER2, were found prognostic for OS (Log-rank p = 0.007, 0.005, 0.009 and 0.043 respectively), and except for FISH HER2, they were also prognostic for TTP Log-rank p = 0.036, 0.068 and 0.066 respectively) in this trastuzumab- treated cohort. Multivariate analysis showed that in the presence of pre-specified set of prognostic factors, among all biomarkers only ECD HER2, as measured by SP3, is strong prognostic factor for both TTP (HR = 0.54, 95% CI: 0.31-0.93, p = 0.027) and OS (HR = 0.39, 95%CI: 0.22-0.70, p = 0.002).
conclusionsThe expression of HER2 ICD and ECD as well as HER2 mRNA levels was significantly associated with TTP and OS in this trastuzumab-treated metastatic cohort. In situ assessment of HER2 mRNA has the potential to identify breast cancer patients who derive benefit from Trastuzumab treatment.
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