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Comprehensive assessment of HER2 alteration in a colorectal cancer cohort: from next-generation sequencing to clinical significance

Authors Yeh YM, Lee CH, Chen SH, Lee CT, Chen YL, Lin BW, Lin SC, Chan RH, Lee JC, Shen MR, Lin PC

Received 24 April 2019

Accepted for publication 6 August 2019

Published 20 August 2019 Volume 2019:11 Pages 7867—7875

DOI https://doi.org/10.2147/CMAR.S213247

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Ahmet Emre Eskazan


Yu-Min Yeh,1,2 Chun-Hui Lee,2 Shang-Hung Chen,2,3 Chung-Ta Lee,4 Yi-Lin Chen,4 Bo-Wen Lin,5 Shao-Chieh Lin,5 Ren-Hao Chan,5 Jenq-Chang Lee,5 Meng-Ru Shen,6,7 Peng-Chan Lin2

1Graduate Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 2Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 3National Institute of Cancer Research, National Health Research Institutes, Hsinchu, Taiwan; 4Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 5Division of Colorectal Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 6Department of Pharmacology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 7Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan

Correspondence: Peng-Chan Lin
Department of Internal Medicine, National Cheng Kung University Hospital, No. 138, Sheng-Li Road, Tainan 704, Taiwan
Tel +886 6 235 3535, ext. 4620
Email pengchanlin@gmail.com

Purpose: Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic target in colorectal cancer (CRC). Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been used to determine HER2-positive CRCs; however, the clinical utility of next-generation sequencing (NGS)-based techniques for determining HER2 status in CRC has been limited. Here, we detail our experience regarding the assessment of HER2 alterations in a CRC cohort.
Materials and methods: We prospectively enrolled 73 CRC patients who underwent surgery and received adjuvant oxaliplatin treatment. We then examined HER2 alterations using the Oncomine Comprehensive Assay version 1, as well as clinical outcomes, in this cohort.
Results: Using the NGS-based assay, HER2 copy number gains in 12 of 73 CRCs were determined to range from 2.74 to 92.62. Of these 12 tumors, 6 had HER2 high-level copy number gain (92.6, 57.9, 57.0, 52.0, 35.2, and 8.42) and were all defined as HER2-positive CRC using HERACLES Diagnostic Criteria. Nevertheless, other 6 patients with low-level copy number gain (ranging from 2.74 to 3.04) and the remaining 61 patients without increase in HER2 copy number were all HER2-negative. Among the 6 HER2-positive CRCs, KRAS and PIK3CA mutations were detected in 1 (17%; G13D) and 2 (33.3%; 1 Q546R and 1 H1047R) patients, respectively. Moreover, 2 of the 6 (33.3%) HER2-positive patients had recurrent disease, while one patient had a partial response after anti-HER2 therapy.
Conclusion: NGS-based tools could assist in the simultaneous detection of HER2 and other genomic alterations in patients with CRC. Only CRCs with HER2 high-level copy number gain were HER2-postive by current diagnostic criteria.

Keywords: HER2, colorectal cancer, next generation sequencing, PIK3CA

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