Detection of ERBB2 Amplification by Next-Generation Sequencing Predicts HER2 Expression in Colorectal Carcinoma.
Am J Clin Pathol
; 152(1): 97-108, 2019 06 05.
Article
em En
| MEDLINE
| ID: mdl-31115453
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Adenocarcinoma
/
Biomarcadores Tumorais
/
Amplificação de Genes
/
Receptor ErbB-2
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article