HER2 copy number as predictor of disease-free survival in HER2-positive resectable gastric adenocarcinoma
Open Access
- 4 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Zeitschrift für Krebsforschung und Klinische Onkologie
- Vol. 147 (5), 1315-1324
- https://doi.org/10.1007/s00432-021-03522-9
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.Funding Information
- Beijing Xisike Clinical Oncology Research Foundation (201008824)
This publication has 52 references indexed in Scilit:
- HER2 expression and its clinicopathological features in resectable gastric cancerGastric Cancer, 2012
- Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinomaHistopathology, 2011
- Combination chemotherapy with S-1 plus cisplatin for gastric cancer that recurs after adjuvant chemotherapy with S-1: multi-institutional retrospective analysisGastric Cancer, 2011
- Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trialThe Lancet, 2010
- Assessment of a HER2 scoring system for gastric cancer: results from a validation studyHistopathology, 2008
- Targeting HER proteins in cancer therapy and the role of the non-target HER3British Journal of Cancer, 2007
- The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesisOncogene, 2007
- Clinical Significance of the Epidermal Growth Factor Receptor and HER2 Receptor in Resectable Gastric CancerAnnals of Surgical Oncology, 2003
- The biology of erbB-2/nue/HER-2 and its role in cancerBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1994
- Tyrosine Kinase Receptor with Extensive Homology to EGF Receptor Shares Chromosomal Location with neu OncogeneScience, 1985