ArticlePloS one2014
Concomitant detection of HER2 protein and gene alterations by immunohistochemistry (IHC) and silver enhanced in situ hybridization (SISH) identifies HER2 positive breast cancer with and without gene amplification.
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 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- HER2 assessment in urothelial carcinoma: standardization challenges and the path forward.Cancer metastasis reviews · 2026Review
- ERBB2-amplified lobular breast carcinoma exhibits concomitant CDK12 co-amplification associated with poor prognostic features.The journal of pathology. Clinical research · 2024Article
- RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding.Journal of experimental & clinical cancer research : CR · 2024Article
- Nicotinamide N-methyltransferase sustains a core epigenetic program that promotes metastatic colonization in breast cancer.The EMBO journal · 2023Article
- Predictive significance of HER2 intratumoral heterogeneity, determined by simultaneous gene and protein analysis, for resistance to trastuzumab-based treatments for HER2-positive breast cancer.Virchows Archiv : an international journal of pathology · 2021Article
- Impact of the Updated Guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Breast Cancer.Journal of breast cancer · 2020Article
- Re-evaluation of HER2 status in 606 breast cancers-gene protein assay on tissue microarrays versus routine pathological assessment.Virchows Archiv : an international journal of pathology · 2020Article
- Post-Operative Complications and Nipple Necrosis Rates Between Conventional and Robotic Nipple-Sparing Mastectomy.Frontiers in oncology · 2020Article
- Neoadjuvant neratinib promotes ferroptosis and inhibits brain metastasis in a novel syngeneic model of spontaneous HER2Breast cancer research : BCR · 2019Article
- Somatic BRCA1 mutations in clinically sporadic breast cancer with medullary histological features.Journal of cancer research and clinical oncology · 2018Article
- Relationship betweenOncoTargets and therapy · 2018Article
- HER2 mRNA transcript quantitation in breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2017Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionHER2 status assessment became a mandatory test assay in breast cancer, giving prognostic and predictive information including eligibility for adjuvant anti-HER2 therapy. Precise and reliable assessment of HER2 status is therefore of utmost importance. In this study we analyzed breast cancer samples by a novel technology for concomitant detection of the HER2 protein and gene copy number.
methodsTissue microarrays containing 589 invasive breast cancer samples were analyzed with a double immunohistochemistry (IHC) and silver labeled in situ hybridization (SISH) assay simultaneously detecting HER2 protein and gene copy number in the same tumor cells. This bright-field assay was analyzed using scores according to the modified ASCO guidelines and the results were correlated with patient prognosis.
resultsOverall concordance rate between protein expression and the presence of gene amplification was 98%. Fifty-seven of 60 tumors (95%) with IHC score 3+, 6 of 10 tumors with IHC score 2+ (60%) and only 3 of 519 tumors (0.6%) with IHC score 0/1+ were amplified by SISH. Patients with gene amplification despite IHC score 0/1+ had a tendency for worse overall survival (p = 0.088, reaching nearly statistical significance) compared to IHC score 0/1+ without amplification. In contrast, there was no difference in overall survival in IHC score 3+/2+ tumors with and without gene amplification.
conclusionsThe novel double IHC and SISH assay for HER2 is efficient in the identification of breast cancer with discordant HER2 protein and HER2 gene status, especially for the prognostically relevant groups of HER2 protein negative tumors with HER2 amplification and HER2 protein positive tumors without HER2 amplification. Breast cancer without HER2 amplification among IHC score 2+/3+ tumors (10% in our cohort) suggests that other mechanisms than gene amplification contribute to protein overexpression in these cells.
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