ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2015
A novel gene-protein assay for evaluating HER2 status in gastric cancer: simultaneous analyses of HER2 protein overexpression and gene amplification reveal intratumoral heterogeneity.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 39 citations in OpenAlex.
- Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer.Scientific reports · 2025Article
- Evolution of HER2-low expression from primary to paired metastatic gastric cancer lesions.NPJ precision oncology · 2025Article
- Molecular classification and intratumoral heterogeneity of gastric adenocarcinoma.Pathology international · 2024Review
- Gastric cancer treatment: recent progress and future perspectives.Journal of hematology & oncology · 2023Review
- A CT-based radiomics signature for prediction of HER2 overexpression and treatment efficacy of trastuzumab in advanced gastric cancer.Translational cancer research · 2022Article
- A multiphase contrast-enhanced CT radiomics model for prediction of human epidermal growth factor receptor 2 status in advanced gastric cancer.Frontiers in genetics · 2022Article
- PTEN is a predictive biomarker of trastuzumab resistance and prognostic factor in HER2-overexpressing gastroesophageal adenocarcinoma.Scientific reports · 2021Article
- Polo-Like Kinase 4's Critical Role in Cancer Development and Strategies for Plk4-Targeted Therapy.Frontiers in oncology · 2021Review
- Impact ofEuropean journal of nuclear medicine and molecular imaging · 2021Article
- Circulating circERBB2 as a potential prognostic biomarker for gastric cancer: An investigative study.Cancer science · 2020Article
- Article
- Clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens in patients with advanced HER2 positive gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2019Article
- Human epidermal growth factor receptor 2-, epidermal growth factor receptor-, and mesenchymal epithelial transition factor-positive sites of gastric cancer using surgical samples.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2019Article
- Quantitative Analysis of HER2 Amplification by Droplet Digital PCR in the Follow-Up of Gastric Cancer Patients Being Treated with Trastuzumab after Surgery.Gastroenterology research and practice · 2019Article
- Clinical impact of intratumoral HER2 heterogeneity on trastuzumab efficacy in patients with HER2-positive gastric cancer.Journal of gastroenterology · 2018Article
- Prognostic implications of HER2 heterogeneity in gastric cancer.Oncotarget · 2018Article
- HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient.Journal of pathology and translational medicine · 2017Article
- Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2017Article
- Coupling CDH17 and CLDN18 markers for comprehensive membrane-targeted detection of human gastric cancer.Oncotarget · 2016Article
- Clinicopathological Characteristics of Patients with Gastric Cancer according to the Expression of LIN28A.Gut and liver · 2016Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman epidermal growth factor receptor 2 (HER2) protein overexpression and gene amplification are important biomarkers for trastuzumab treatment in breast and gastric cancer patients. Gastric cancer presents high rates of tumor heterogeneity, which may influence the results of HER2 testing. A novel gene-protein assay (GPA) can allow the simultaneous analysis of HER2 protein and gene status on a single slide.
methodsUsing the tissue microarray technique, the HER2 status of each of 875 gastric cancer cases was evaluated by immunohistochemistry (IHC), brightfield dual-color in situ hybridization (DISH), and GPA. Intratumoral phenotypic and genotypic heterogeneity were evaluated by comparing the HER2 statuses of two tissue cores from each case.
resultsThere was excellent concordance between GPA and IHC (99.2 %), as well as between GPA and DISH results (99.3 %). HER2 positivity obtained by GPA was almost identical (99.8 %) to the results obtained by IHC and DISH assays. Intratumoral phenotypic heterogeneity was more frequently observed in IHC 2+ cases (63.5 %) compared with IHC 3+ cases (28.3 %). Phenotypic heterogeneity (48.8 %) was more frequently observed than genotypic heterogeneity (26.8 %). Tumor heterogeneity was consistently observed from early to advanced stages.
conclusionsHER2-positive gastric cancers presented different levels of HER2 protein expression and gene amplification statuses within the same lesion in almost half the cases examined. Evaluating both phenotypic and genotypic heterogeneity may contribute to a deeper understanding and improved prediction of clinical outcome in gastric cancer patients treated with trastuzumab. This newly established GPA technology may also be useful for developing biomarkers for other molecularly targeted therapies.
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