Detection of ERBB2 Amplification by Next-Generation Sequencing Predicts HER2 Expression in Colorectal Carcinoma
| Autor: | Jason L. Hornick, Lynette M. Sholl, Azra H. Ligon, Odise Cenaj |
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| Rok vydání: | 2019 |
| Předmět: |
clone (Java method)
Receptor ErbB-2 Colorectal cancer Adenocarcinoma Biology Lapatinib DNA sequencing 03 medical and health sciences 0302 clinical medicine Trastuzumab Biomarkers Tumor medicine Humans skin and connective tissue diseases neoplasms In Situ Hybridization Fluorescence medicine.diagnostic_test Gene Amplification High-Throughput Nucleotide Sequencing General Medicine medicine.disease Immunohistochemistry Molecular biology ERBB2 Amplification 030220 oncology & carcinogenesis Colorectal Neoplasms 030215 immunology Fluorescence in situ hybridization medicine.drug |
| Zdroj: | American Journal of Clinical Pathology. 152:97-108 |
| ISSN: | 1943-7722 0002-9173 |
| DOI: | 10.1093/ajcp/aqz031 |
| Popis: | Objectives ERBB2 (human epidermal growth factor receptor 2 [HER2]) amplification/overexpression in colorectal carcinomas (CRCs) may predict response to HER2 inhibitors. We correlated ERBB2 amplification by next-generation sequencing (NGS) with HER2 overexpression by immunohistochemistry. Methods NGS was performed on specimens containing 20% or more tumor. HER2 immunohistochemistry (clone SP3) was scored semiquantitatively by H-score. ERBB2 fluorescence in situ hybridization (FISH) was performed to examine copy alterations in one HER2-heterogeneous tumor. Results ERBB2 amplification was detected in 2% of 1,300 CRCs analyzed by NGS. HER2 immunohistochemistry was examined in 15 cases with ERBB2 amplification (six or more copies), 10 with low gain (three to five copies), and 77 copy neutral. ERBB2 amplification and HER2 immunohistochemistry showed perfect concordance at an H-score of 105 or more. FISH confirmed homogeneous ERBB2 amplification in a tumor showing HER2 protein expression heterogeneity. ERBB2 amplification anticorrelated with RAS/RAF mutations (P = .0001). No ERBB2-amplified cases showed mismatch repair deficiency. Conclusions NGS-detected ERBB2 amplification highly correlates with HER2 overexpression in CRC, but immunohistochemistry is required to capture protein-level heterogeneity. |
| Databáze: | OpenAIRE |
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