PMID- 31692488 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220411 IS - 1179-1322 (Print) IS - 1179-1322 (Electronic) IS - 1179-1322 (Linking) VI - 11 DP - 2019 TI - Comprehensive assessment of HER2 alteration in a colorectal cancer cohort: from next-generation sequencing to clinical significance. PG - 7867-7875 LID - 10.2147/CMAR.S213247 [doi] AB - 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. CI - (c) 2019 Yeh et al. FAU - Yeh, Yu-Min AU - Yeh YM AD - Graduate Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Lee, Chun-Hui AU - Lee CH AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Chen, Shang-Hung AU - Chen SH AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. AD - National Institute of Cancer Research, National Health Research Institutes, Hsinchu, Taiwan. FAU - Lee, Chung-Ta AU - Lee CT AD - Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Chen, Yi-Lin AU - Chen YL AD - Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Lin, Bo-Wen AU - Lin BW AD - Division of Colorectal Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Lin, Shao-Chieh AU - Lin SC AD - Division of Colorectal Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Chan, Ren-Hao AU - Chan RH AD - Division of Colorectal Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Lee, Jenq-Chang AU - Lee JC AD - Division of Colorectal Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Shen, Meng-Ru AU - Shen MR AD - Department of Pharmacology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. AD - Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Lin, Peng-Chan AU - Lin PC AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. LA - eng PT - Journal Article DEP - 20190820 PL - New Zealand TA - Cancer Manag Res JT - Cancer management and research JID - 101512700 PMC - PMC6708395 OTO - NOTNLM OT - HER2 OT - PIK3CA OT - colorectal cancer OT - next generation sequencing COIS- The authors report no conflicts of interest in this work. EDAT- 2019/11/07 06:00 MHDA- 2019/11/07 06:01 PMCR- 2019/08/20 CRDT- 2019/11/07 06:00 PHST- 2019/04/24 00:00 [received] PHST- 2019/08/06 00:00 [accepted] PHST- 2019/11/07 06:00 [entrez] PHST- 2019/11/07 06:00 [pubmed] PHST- 2019/11/07 06:01 [medline] PHST- 2019/08/20 00:00 [pmc-release] AID - 213247 [pii] AID - 10.2147/CMAR.S213247 [doi] PST - epublish SO - Cancer Manag Res. 2019 Aug 20;11:7867-7875. doi: 10.2147/CMAR.S213247. eCollection 2019.