HER2 copy number as predictor of disease-free survival in HER2-positive resectable gastric adenocarcinoma.

Zimin Liu, Mingpeng Shi, Xiaoxiao Li, Shanai Song, Ning Liu, Haiwei Du, Junyi Ye, Haiyan Li, Zhou Zhang, Lu Zhang

Journal of cancer research and clinical oncology 2021 May

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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. 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. 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. 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.

Citation

Zimin Liu, Mingpeng Shi, Xiaoxiao Li, Shanai Song, Ning Liu, Haiwei Du, Junyi Ye, Haiyan Li, Zhou Zhang, Lu Zhang. HER2 copy number as predictor of disease-free survival in HER2-positive resectable gastric adenocarcinoma. Journal of cancer research and clinical oncology. 2021 May;147(5):1315-1324