HER2 copy number as predictor of disease-free survival in HER2-positive resectable gastric adenocarcinoma.
J Cancer Res Clin Oncol
; 147(5): 1315-1324, 2021 May.
Article
in En
| MEDLINE
| ID: mdl-33543328
ABSTRACT
PURPOSE:
The identification of HER2 overexpression in a subset of gastric adenocarcinoma (GA) patients represents a significant step forward in unveiling the molecular complexity of this disease. The predictive and prognostic value of HER2 amplification in advanced HER2 inhibitor-treated GA patients has been investigated. However, its predictive value in resectable patients remains elusive.METHODS:
We enrolled 98 treatment-naïve resectable Chinese GA patients with HER2 overexpression assessed using IHC. Capture-based targeted sequencing using a panel consisting of 41 gastrointestinal cancer-related genes was performed on tumor tissues. Furthermore, we also investigated the correlation between HER2 copy number (CN) and survival outcomes.RESULTS:
Of the 98 HER2-overexpressed patients, 90 had HER2 CN amplification assessed using next-generation sequencing, achieving 92% concordance. The most commonly seen concurrent mutations were occurring in TP53, EGFR and PIK3CA. We found HER2 CN as a continuous variable was an independent predictor associated with DFS (p = 0.029). Our study revealed HER2 CN-high patients showed a trend of intestinal-type GA predominant (p = 0.075) and older age (p = 0.07). The median HER2 CN was 15.34, which was used to divide the cohort into CN-high and CN-low groups. Patients with high HER2 CN had a significantly shorter DFS than patients with low HER2 CN (p = 0.002). Furthermore, HER2 CN as a categorical variable was also an independent predictor associated with DFS in patients.CONCLUSION:
We elucidated the mutation spectrum of HER2-positive resectable Chinese GA patients and the association between HER2 CN and DFS. Our work revealed HER2 CN as an independent risk factor predicted unfavorable prognosis in HER2-positive GA patients and allowed us to further stratify HER2-positive resectable GA patients for disease management.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
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Adenocarcinoma
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Receptor, ErbB-2
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DNA Copy Number Variations
Type of study:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Cancer Res Clin Oncol
Year:
2021
Document type:
Article
Affiliation country: