ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2016
Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
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- Comprehensive genomic landscape of ERBB2 in Chinese GI tumors: mutation-centered landscapes and precision treatment opportunities.Therapeutic advances in medical oncology · 2026Article
- Clinical Proteomics for Solid Organ Tissues.Molecular & cellular proteomics : MCP · 2023Article
- Protein Profiling in Human Papillomavirus-Associated Cervical Carcinogenesis: Cornulin as a Biomarker for Disease Progression.Current issues in molecular biology · 2023Article
- HER2 Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Highly Accurate and Robust Absolute Quantification of Target Proteins in Formalin-Fixed Paraffin-Embedded (FFPE) Tissues by LC-MS.Analytical chemistry · 2023Article
- A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification.Frontiers in oncology · 2023Article
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- Putative Clinical Potential ofCancers · 2022Article
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- Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Targeted multiplex proteomics for molecular prescreening and biomarker discovery in metastatic colorectal cancer.Scientific reports · 2019Article
- Impact of proteomics investigations on gastric cancer treatment and diagnosis.Gastroenterology and hepatology from bed to bench · 2019Review
- Development of parallel reaction monitoring (PRM)-based quantitative proteomics applied to HER2-Positive breast cancer.Oncotarget · 2018Article
- Circulating HER-2 mRNA in the peripheral blood as a potential diagnostic and prognostic biomarker in females with breast cancer.Oncology letters · 2018Article
- Targeted Therapies for Targeted Populations: Anti-EGFR Treatment forCancer discovery · 2018Article
- Reproducible proteomics sample preparation for single FFPE tissue slices using acid-labile surfactant and direct trypsinization.Clinical proteomics · 2018Article
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20 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundTrastuzumab has shown a survival benefit in cases of Her2-positive gastroesophageal cancer (GEC). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) currently determine eligibility for trastuzumab-based therapy. However, these low-throughput assays often produce discordant or equivocal results.
methodsWe developed a targeted proteomic assay based on selected reaction monitoring mass spectrometry (SRM-MS) and quantified levels (amol/μg) of Her2-SRM protein in cell lines (n = 27) and GEC tissues (n = 139). We compared Her2-SRM protein expression with IHC/FISH, seeking to determine optimal SRM protein expression cutoffs in order to identify HER2 gene amplification.
resultsAfter demonstrating assay development, precision, and stability, Her2-SRM protein measurement was observed to be highly concordant with the HER2/CEP17 ratio, particularly in a multivariate regression model adjusted for SRM expression of the covariates Met, Egfr, Her3, and HER2 heterogeneity, as well as their interactions (cell lines r (2) = 0.9842; FFPE r (2) = 0.7643). In GEC tissues, Her2-SRM protein was detected at any level in 71.2 % of cases. ROC curves demonstrated that Her2-SRM protein levels have a high specificity (100 %) at an upper-level cutoff of >750 amol/µg and sensitivity of 75 % at a lower-level cutoff of <450 amol/μg for identifying HER2 FISH-amplified tumors. An "equivocal zone" of 450-750 amol/µg of Her2-SRM protein was analogous to IHC2+ but represented fewer cases (9-16 % of cases versus 36-41 %).
conclusionsCompared to IHC, targeted SRM-Her2 proteomics provided more objective and quantitative Her2 expression with excellent HER2/CEP17 FISH correlation and fewer equivocal cases. Along with its multiplex capability for other relevant oncoproteins, these results demonstrate a refined HER2 protein expression assay for clinical application.
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