Detection of ERBB2 Amplification by Next-Generation Sequencing Predicts HER2 Expression in Colorectal Carcinoma

• Published in: American journal of clinical pathology Vol. 152; no. 1; pp. 97 - 108
• Main Authors: Cenaj, Odise, Ligon, Azra H, Hornick, Jason L, Sholl, Lynette M
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 05.06.2019
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Care and treatment; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Development and progression; Epidermal growth factor; ErbB-2 protein; Fluorescence in situ hybridization; Gene Amplification; Gene expression; Genetic aspects; Health aspects; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Immunotherapy; In Situ Hybridization, Fluorescence; Inhibitor drugs; Mismatch repair; Monoclonal antibodies; Next-generation sequencing; Raf protein; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Targeted cancer therapy; United States; Amplification; Immunohistochemistry; Next-generation sequencing; Colorectal carcinoma; Colon; NGS; Lapatinib; HER2; Trastuzumab; ERBB2
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/ajcp/aqz031

ABSTRACT 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.