ERBB2 Comprehensive Profiling and Prognostication in Stage III Colon Cancer: Findings From PETACC8 and IDEA-France Cohorts
Résumé
BACKGROUND & AIMS: ERBB2 pathway activation, through amplification or activating mutations, represents a new target for colon cancer (CC) treatment. Molecular methods were compared with the gold standard for assessing ERBB2 status, and the prognostic value of ERBB2 amplification, mutations, and expression was determined using data from 2 phase 3 trials involving nearly 3000 patients with stage III CC. METHODS: In the PETACC8 trial, immunohistochemistry and fluorescence in situ hybridization, DNA, and RNA analysis were performed on 1813, 1719, and 1733 samples, respectively. In the IDEA-France trial, DNA and RNA sequencing was performed on 1129 and 1263 samples. The breast cancer SCAN-B cohort (N ¼ 3409) served as an external reference. A new molecular ERBB2-amplified status was defined using ERBB2 nextgeneration sequencing score, RNA sequencing expression, and clustering based on ERBB2 neighboring gene expression. Concordance between diagnostic techniques and the association between time to recurrence (TTR) and ERBB2-status were Gastroenterology 2024;-:1-11 evaluated. RESULTS: The prevalence of the molecular ERBB2amplified group was 1.85% in PETACC8 and 1.5% in IDEA-France, with a concordance of 0.81 (95% CI, 0.70-0.92) with the gold standard immunohistochemistry and fluorescence in situ hybridization method in PETACC8. A nonlinear relationship was observed between TTR and ERBB2 expression, with extreme groups showing a less favorable prognosis (P < .0001) in both colon and breast cancers. Patients with molecular ERBB2-amplified status or mutations had the poorest prognosis, followed by low-expression and intermediate-expression groups (3-year TTR of 67.0%, 71.2%, and 77.9%, respectively). In multivariate analysis, the low-expression group had a significantly shorter TTR (hazard ratio, 1.28; 95% CI, 1.07-1.52). CONCLUSIONS: The molecular definition of ERBB2 status could represent a cost-effective alternative in stage III CC. ERBB2 alterations and low RNA expression significantly reduced TTR, highlighting the complex role of ERBB2.
Mots clés
HER2 Amplification ERBB2 Expression IHC/FISH RNA-seq NGS Score Stage III CC Prognosis CC
colon cancer CMS
consensus molecular subtype EGFR
epidermal growth factor receptor FFPE
formalin-fixed
paraffin-embedded FISH
fluorescence in situ hybridization FOLFOX4
oxaliplatin
leucovorin
and 5-fluorouracil HR
hazard ratio IHC
immunohistochemistry NGS
next-generation sequencing RNAseq
RNA sequencing TTR
time to recurrence
HER2 Amplification
ERBB2 Expression
IHC/FISH
RNA-seq
NGS Score
Stage III CC Prognosis CC
colon cancer
CMS
consensus molecular subtype
EGFR
epidermal growth factor receptor
FFPE
paraffin-embedded
FISH
fluorescence in situ hybridization
FOLFOX4
and 5-fluorouracil
HR
hazard ratio
IHC
immunohistochemistry
NGS
next-generation sequencing
RNAseq
RNA sequencing
TTR
Domaines
Sciences du Vivant [q-bio]Origine | Publication financée par une institution |
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licence |